Role of intestinal excretion in the effect of subcutaneously administered sedecamycin on cecal infection caused by Treponema hyodysenteriae in mice

Abstract

The therapeutic effects of subcutaneously administered sedecamycin on experimental Treponema hyodysenteriae infection in mice were evaluated. Sedecamycin was more active than tiamulin and lincomycin. The efficacy of sedecamycin upon subcutaneous administration was similar to that upon oral administration. Sedecamycin given subcutaneously provided similar degrees of protection in bile duct-ligated and intact mice. Pharmacokinetic studies utilizing a liquid chromatographic technique were carried out to determine the concentration of sedecamycin in the cecum, the site of T. hyodysenteriae infection in mice. Little sedecamycin was found; however, lankacidinol, a major metabolite of sedecamycin, was found in the cecal contents of intact mice after subcutaneous or oral administration of sedecamycin. Lankacidinol was also found in the cecal contents of bile duct-ligated mice, although the concentration found after subcutaneous administration of sedecamycin was much lower than that found after subcutaneous or oral administration to intact mice. These results indicate that sedecamycin is excreted directly into the intestinal tract as an active metabolite by a route other than the bile duct. It is suggested that this intestinal excretion plays an important role in the efficacy of subcutaneously administered sedecamycin against cecal infection of mice by T. hyodysenteriae.Treponema hyodysenteriae, the etiologic agent of swine dysentery, is characterized by mucohemorragic diarrhea (9,25). In general, severely infected animals are reluctant to consume the medicated feed. In such cases, parenteral administration of effective drugs, lincomycin (8) and tiamulin (1, 2), is used for treatment. Swine dysentery is infection with T. hyodysenteriae in the large intestine (5, 10); therefore, a sufficient amount of a drug must be distributed to the large intestine. When a drug is administered parenterally, the route by which it is distributed to the large intestine is thought to be biliary and intestinal excretion. Recently, intestinal excretion has become a well-recognized phenomenon (3,4,7,13,22). However, little is known about the pharmacokinetics of injectable drugs for swine dysentery in relation to efficacy.Experimental infection of mice and rabbits with T. hyodysenteriae had failed until Joens and Glock (14) reported that CF1 mice inoculated with T. hyodysenteriae for 2 consecutive days after a 72 h of fasting developed cecal and colonic lesions. Later, Suenaga and Yamazaki (24) reported that they examined mouse strains and found that Ta:CF#1 mice developed gross cecal lesions after a single oral administration of T. hyodysenteriae without fasting. By using this animal model, we have shown that orally administered sedecamycin, a 17-member macrocyclic antibiotic ( Fig. 1), shows good efficacy in mice (11).The objective of this study was to evaluate the efficacy of subcutaneous administration of sedecamycin against experimental infection of mice with T. hyodysenteriae and to explain the mechanisms of the efficacy by the concentra...

Excretion of ciprofloxacin into the large bowel of the rabbit

“…The possibility that a paracellular diffusion process is responsible for the colonic elimination of ciprofloxacin can probably be ruled out because [ 3 H]inulin was neither absorbed nor secreted from or into the colon. This recapitulates the findings from previous studies of fluoroquinolones elimination in the small bowel (5,13,16). A carryover effect of ciprofloxacin from the small bowel can also be ruled out since neither the cecal segment nor the other segments in the large bowel had continuity with the more proximal segments.…”

Sensitivity of strains of Serpulina hyodysenteriae isolated in Hungary to chemotherapeutic drugs

“…Very few data are available on sedecamycin, which belongs to the group of macrolide antibiotics and has a bactericidal effect only on S hyodysenteriae. In field experiments carried out in Hungary very good results have been observed, but the in vitro results (Table 3) were much poorer than those published by Hayashi and others (1991). On account of its rapid clearance, sedecamycin may play an important role in the treatment of pigs just before they are slaughtered.…”

“…The control of swine dysentery in affected herds is based on improving the diet and hygienic conditions and very often on drug therapy. The sensitivity of strains of Serpulina hyodysenteriae to chemotherapeutic drugs has been studied by many authors including Hayashi and others (1991), Messier (1992) and Gunnarsson and Franklin (1992). The results of the investigations have often been similar (Walter and Kinyon 1990, Smith and others 1991) but sometimes they have been very different (Messier and others 1990, Ronne and Szancer 1990).…”