Potential Therapeutic Effects of Mepacrine against Clostridium perfringens Enterotoxin in a Mouse Model of Enterotoxemia.

Clostridium perfringens enterotoxin (CPE) is a pore-forming toxin that causes the symptoms of common bacterial food poisoning and several non-foodborne human gastrointestinal diseases, including antibiotic-associated diarrhea and sporadic diarrhea. In some cases, CPE-mediated disease can be very severe or fatal due to the involvement of enterotoxemia. Therefore, the development of potential therapeutics against CPE action during enterotoxemia is warranted. Mepacrine, an acridine derivative drug with broad-spectrum effects on pores and channels in mammalian membranes, has been used to treat protozoal intestinal infections in human patients. A previous study showed that the presence of mepacrine inhibits CPE-induced pore formation and activity in enterocyte-like Caco-2 cells, reducing the cytotoxicity caused by this toxin in vitro Whether mepacrine is similarly protective against CPE action in vivo has not been tested. When the current study evaluated whether mepacrine protects against CPE-induced death and intestinal damage using a murine ligated intestinal loop model, mepacrine protected mice from the enterotoxemic lethality caused by CPE. This protection was accompanied by a reduction in the severity of intestinal lesions induced by the toxin. Mepacrine did not reduce CPE pore formation in the intestine but inhibited absorption of the toxin into the blood of some mice. Protection from enterotoxemic death correlated with the ability of this drug to reduce CPE-induced hyperpotassemia. These in vivo findings, coupled with previous in vitro studies, support mepacrine as a potential therapeutic against CPE-mediated enterotoxemic disease.

A survey of Clostridium spiroforme antimicrobial susceptibility in rabbit breeding.

Rabbit meat breeding may be heavily affected by enterotoxaemia due to Clostridium spiroforme. Data on its antimicrobial susceptibility are insufficient, presumably because of difficulties in cultivating and identifying the pathogen. Our aim is therefore to provide this information to veterinary practitioners by focusing on a panel of therapeutics used in intensive rabbit units. Lincomycin was also checked in order to investigate the origin of resistance to macrolides. Minimal inhibitory concentrations (MICs) were determined with the agar dilution method according to the CLSI M11-A7 protocol (2007). MIC(50) and MIC(90) were, respectively, 64 and 64microg/ml for tiamulin, 32 and 32microg/ml for norfloxacin, 0.063 and 0.125microg/ml for amoxicillin, and 8 and 16microg/ml for doxycycline. MIC(50) and MIC(90) were 256microg/ml for sulphadimethoxine, spiramycin and lincomycin. Our results have shown that intrinsic or acquired antimicrobial resistances are diffuse in the C. spiroforme population and suggest focusing on prevention rather than on treatment of clostridial overgrowth, by reducing risk factors and using antimicrobials prudently.

[The characteristics of the development of bacterial enterotoxemia and endotoxemia in combined radiation and thermal lesions]. / Osobennosti razvitiia bakterial'noi énteroéndotoksemii pri kombinirovannykh radiatsionno-termicheskikh porazheniiakh.

Thermal burn of irradiated rats increases the level and the length of the postirradiation enteroendotoxemia and aggravates the postirradiation impairment of the hematoenterocitic barrier. The pharmacological correction of the small intestine motility and introduction of ciproheptadine, an agent that blocks serotonin receptors, ameliorates the above phenomenon in radiation and thermal injuries.

Enterotoxemia in neonatal calves.

The incidence, bacterial characteristics, disease syndromes, diagnosis, treatment, and prevention of enterotoxemia of neonatal calves caused by Clostridium perfringens (Types A, B, C, D, and E) are reviewed.

[Studies of necrotizing enteritis of suckling piglets (Clostridium perfringens type C enterotoxemia) in industrialized sow breeding units. 5. Control of the disease]. / Untersuchungen zur nekrotisierenden Enteritis der Saugferkel (Clostridium-perfringens-Typ-C-Enterotoxämie) in industriemässig produzierenden Sauenzuchtanlagen. 5. Mitteilung: Bekämpfung der Krankheit.

Recent methods used and experience obtained in the control of necrotising enteritis are reported in this paper, with reference being made to both the pathogenesis and epizootiology of the disease. Two inoculations of the sows, using "Enterotoxämievakzine Dessau bivalent" five and three weeks before parturition, have worked well for prophylaxis. Oral treatment was applied to nursed piglets, using 40,000 I.U. of "Aviapen" and "V-Tablopen" penicillin per animal and day over periods between two and four days, helped to minimise piglet loss, particularly in the period between a fresh outbreak and full effectiveness of immunoprophylactic action. Such treatment was conducted metaphylactically and therapeutically. The first metaphylactic treatment was given within 24 hours from parturition. Combination of mother animal vaccination with the above therapeutic use of those two penicillin preparations worked extremely well in enzootically contaminated stocks and proved to be the most effective approach, for the time being, to controlling necrotising enteritis of nursed piglets. Yet, all those control measures failed to bring about full stock sanitation on industrialised units. Sow trading was not permitted until at least four weeks had elapsed from full effectiveness of mother animal vaccination, with the view to reducing the proliferation of Clostridium perfringens Type C via sales of breeding animals. All sows were given two "Enterotoxämievakzine Dessau bivalent" vaccinations, prior to sale. The animals were sold only to smaller farms (less than 500 sows for breeding) with concentional keeping patterns which were kept under constant diagnostic supervision. Neomycin, oxytetracycline, chloramphenicol, and other antibiotics against which Clostridium perfringens was resistant or in a position to assume resistance were used on endangered stocks only in conjunction with penicillin or not at all. This programme of control has proved to be efficient through a period of more than three years.