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Label and extra label drug use in small ruminants.

The small ruminant practitioner has a small arsenal of approved drugs in the United States, so the practitioner must be familiar with the laws and regulations related to extra label use. Drugs can be used extra label in food animals only under specific circumstances and can be used only for therapeutic purposes. Drugs that are illegal in small ruminants include chloramphenicol; clenbuterol; diethylstilbestrol; dimetridazole, ipranidazole, and other nitroimidazoles such as metronidazole; dipyrone; fluoroquinolones; glycopeptides; nitrofurans; furazolidone; and extra label use of medication in feed. It is also illegal to use any drug that results in residues above established tolerances or safe levels.

Animals↗

Deposition and depletion of five anticoccidials in eggs.

Anticoccidials are compounds that are widely used as feed additives to prevent and treat coccidiosis. They are licensed for use in a prescribed concentration and during a certain time interval for broilers and pullets but not for laying hens. It was shown in the past that carry-over at the feeding mill is found to be the main reason for the presence of residues in eggs. An animal experiment was set up to investigate the effect of carry-over at the feeding mill on the presence of residues of anticoccidials in eggs. For the compounds diclazuril, robenidine, halofuginone and nicarbazin in combination with narasin, two concentration levels were tested: the maximum allowed concentration for broilers (100%) and a concentration corresponding to 5% carry-over during feed preparation. Also dimetridazole was included in the experiment but only at one concentration level. Eggs were sampled during treatment (14 days) and for a period of 30 days after withdrawal of the anticoccidial-containing feed. Residues were determined, and deposition and depletion curves were generated. Analyses were performed by ELISA and LC-MS/MS. For all compounds, substantial residues could be found in the 5% groups, which points out the risk of carry-over at the feeding mill. The distribution of the residues between egg yolk and white was determined by analyzing both fractions.

Animal Feed↗

Incidence of residues of nine anticoccidials in eggs.

A survey of the presence of residues of anticoccidials was performed. Three hundred and twenty egg samples, purchased in eight different European countries, were analysed for the presence of nine different compounds: dimetridazole, diclazuril, halofuginone, robenidine, nicarbazin, narasin, salinomycin, lasalocid and monensin. Analyses were performed by LC-MS/MS. Of the samples analysed, 114 (35.6%) contained one or more of the nine anticoccidials in concentrations ranging from 0.1 to 63 microg kg-1. Salinomycin and lasalocid account for more than 60% of all positive samples. Almost 90% of all positive samples contained less than 2 microg kg-1. Results were put into perspective of the farming method and country of origin.

Animal Husbandry↗

Toxicity in utility pigeons caused by the coccidiostat dinitolmide.

Utility pigeons on 3 farms were affected by a severe neurological disturbance manifested by fine tremors, rolling gait and incoordination. Affected birds had necrosis of the Purkinje cells of the cerebellar cortex. The birds from the 3 farms had been fed a pelleted diet obtained from a single mix of feed prepared by a stockfeed manufacturer. When feed obtained from the farms was given to utility pigeons under controlled conditions at the laboratory, they suffered the same clinical signs and lesions as seen in birds from the farms. Cross-bred cockerels were not affected when given this feed from day-old to 6 weeks of age. Samples of the feed contained 185 to 226 ppm of the coccidiostat dinitolmide. Utility pigeons given a prepared diet containing a similar level (234 ppm) of dinitolmide developed an identical condition after 3 to 4 weeks feeding. Laying hens were not affected by this feed. Dimetridazole, which was also present in some of the original feed samples, did not exacerbate the condition when included in the diet at a rate of 233 ppm. Production of squabs from the affected farms was dramatically reduced, and many of the breeder had to be culled because of the long-standing neurological disease.

Animal Feed↗

Spironucleosis in Australian king parrots (Alisterus scapularis).

OBJECTIVE: To describe a syndrome of wasting, diarrhoea and mortality in Australian king parrots (Alisterus scapularis). DESIGN: Field observations and laboratory examinations. Procedure Pathological examinations were performed on 50 Australian king parrots with wasting and diarrhoea. Wet preparations of intestinal contents were examined by light microscopy. Tannins were extracted from acorns (Quercus sp) and tested for toxicity in mice. CLINICAL SIGNS AND EPIDEMIOLOGY: A syndrome of wasting, diarrhoea and mortality was observed in wild juvenile Australian king parrots in eastern Australia from 1984 to 2000. Sporadic cases and outbreaks of disease occurred from May to September in New South Wales, the Australian Capital Territory and Victoria. Outbreaks in the Australian Capital Territory in 1990 and 1991 were associated with parrots congregating to feed on acorns. Most affected birds failed to respond to treatment with dimetridazole and died 1 to 14 days after hospitalisation. Selected cases recovered following treatment with metronidazole. PATHOLOGY: Affected birds were emaciated, with faecal matting of feathers around the cloaca and yellow-green fluid, foamy intestinal contents. Abundant motile Spironucleus trophozoites were observed in wet preparations of faeces of clinically affected birds and intestinal contents of birds examined within 1 h of death. Protozoa were detected histologically in crypts of Lieberkühn in the intestine in association with exudation of mucus (catarrhal enteritis) or lymphoplasmacytic enteritis. Toxicology Tannin extracts from acorns induced periacinar hepatic necrosis in mice. CONCLUSION: Wasting, diarrhoea and mortality in wild juvenile Australian king parrots were associated with Spironucleus-like protozoa in the intestine. Acorns were not considered to be the cause of the syndrome.

Animals↗

Antitrichomonad action, mutagenicity, and reduction of metronidazole and other nitroimidazoles.

Twelve 4- and 5-nitroimidazole derivatives, including metronidazole and two of its metabolites, tinidazole, dimetridazole, and nimorazole, were tested for antitrichomonad action on Tritrichomonas foetus (KV(1)) and Trichomonas vaginalis (ATCC 30001) for mutagenicity on a nitroreductase-positive (TA 100) and a nitroreductase-deficient (TA 100-FR(1)) strain of Salmonella typhimurium, as well as for the reducibility of the nitro group by T. foetus homogenates. Compounds with activity <1% of that of metronidazole are regarded as inactive. All antitrichomonad compounds induce mutations and can be reduced. S. typhimurium TA 100 gave mutations under both aerobiosis and anaerobiosis; TA 100-FR(1), however, gave mutations only under anaerobiosis. Certain compounds that are reducible, and the nonreducible derivatives, were inactive. Metronidazole and its inactive 4-nitro analogue were reduced in a four-electron process in ferredoxin- or methyl viologen-mediated reactions with the same velocity. The results underscore the role of the reduction of the nitro group in the antitrichomonad and in the mutagenic activity of nitroimidazoles.

Aerobiosis↗

In vitro activities of 47 antimicrobial agents against three Campylobacter spp. from pigs.

The in vitro activities of 47 antimicrobial agents against 30 isolates of Campylobacter species from pigs were determined by the agar dilution technique. The isolates were obtained from pigs with proliferative enteritis and included 10 strains each of Campylobacter coli, Campylobacter sputorum subsp. mucosalis, and "Campylobacter hyointestinalis Gebhart et al." (this name is not on the Approved Lists). Carbadox, furazolidone, nitrofurantoin, gentamicin, and dimetridazole were the most active drugs, inhibiting all three Campylobacter species with a MIC for 50% of the isolates of 2 micrograms/ml or less. Trimethoprim-sulfamethoxazole, cefazolin, sulfachloropyridazine, novobiocin, vancomycin, sulfathiazole, cyclohexamide, bacitracin, p-arsanilic acid, and colistin were the least active, with MICs for 50% of the isolates ranging from 16 to greater than or equal to 128 micrograms/ml.

Animals↗

Synergism between Trichuris suis and the microbial flora of the large intestine causing dysentery in pigs.

The role of the microbial flora of the large intestine in experimental Trichuris suis infection was studied by comparing the clinical syndrome in conventionally reared (CR) pigs, specific pathogen-free pigs, and gnotobiotic pigs. Thedisease in CR pigs was characterized by a severe mucohemorrhagic enteritis; in contrast, a mild catarrhal enteritis was observed in specific pathogen-free and gnotobiotic pigs. Spirochaetes and vibrio-like organisms were observed only in CR pigs and increased during the clinical phase of the disease. The clinical syndrome was not transmitted by oral administration of intestinal or fecal material from infected CR pigs to CR pigs free of T. suis. Smaller numbers of T. suis produced diarrhea in CR pigs and significantly reduced the growth rates of infected animals; clinical signs and the reduction in growth rate was prevented by incorporating an antibacterial substance (dimetridazole) in the food. Although clinical trichuriasis closely resembles swin dysentery, the two syndromes seem to be distinct. The present results suggest that a microbial component acts synergistically with T. suis to produce the severe clinical syndrome in CR pigs, but identification of the microbial component and the mechanism by which clinical signs are produced await further studies of the bacterial flora of the large intestine of pigs.

Animals↗

Some unusual diseases in the birds of Victoria, Australia.

The following unusual diseases were diagnosed in birds submitted to the Veterinary Research Institute, Victoria, between 1978 and 1987: the viral diseases beak and feather disease of psittacines, infectious laryngotracheitis in peafowls, a papovavirus-like inclusion body disease in psittacines, and pox; chlamydiosis; the bacterial diseases actinomycosis, listeriosis and mycobacteriosis; the fungal diseases favus, yeast infections and systemic zygomycosis; the protozoan diseases cryptosporidiosis, hexamitiasis, suspected leucocytozoonosis, sarcosporidiosis, toxoplasmosis, trichomoniasis and an unidentified protozoan-like organism which caused pneumonia in ducks; a variety of parasites; the metabolic disorders curled-toe paralysis in pheasant poults, encephalomalacia and parenchymatous goitre; toxicity due to dimetridazole and the ingestion of the leaves of the tobacco tree; and other non-infectious conditions including asphyxiation, burns, cataracts, cerebellar degeneration and atrophy, cystic right oviducts and exertional rhabdomyolysis.

Animals↗

In vitro susceptibility and a new point mutation associated with tylosin-resistance in Japanese canine intestinal spirochetes.

The in vitro susceptibilities of six commonly used antimicrobial agents against 29 isolates of intestinal spirochetes isolated from dogs in Japan were examined by the agar dilution technique. In addition, the genetic basis of tylosin resistance in in vitro selected resistant mutants of two reference strains and three tylosin-susceptible field isolates obtained by three successive subcultures on blood agar containing 1 microg/ml of tylosin was investigated. Carbadox was the most active (MIC: < 0.00625) of all the antimicrobial agents. Although all the isolates were susceptible to tylosin, some were resistant to erythromycin. Tiamulin, lincomycin and dimetridazole were also very active against the isolates. All the resistant isolates did not harbor any plasmids. In vitro selected tylosin-resistant mutants of previously tylosin-susceptible isolates showed a new mutation in which their adenine at the base position equivalent to 2062 of 23S rDNA of Escherichia coli has been replaced by cytosine. These findings may both provide guidance towards the proper choice of antimicrobial agents for the treatment of canine intestinal spirochetosis, and add to the understanding of the genetic basis of tylosin resistance.

Animals↗

In vitro susceptibility of 21 antimicrobial agents to 37 isolates of Brachyspira hyodysenteriae isolated from pigs in Okinawa Prefecture.

The in vitro susceptibilities to 21 antimicrobial agents, of 37 isolates of Brachyspira (B.) hyodysenteriae isolated from pigs in Okinawa meat center and a pig farm in Okinawa Prefecture, Japan, were determined by the agar dilution method. Carbadox was the most active of all the agents tested against the isolates (MIC: <0.003 to 0.05). All the isolates were highly susceptible to olaquindox, tiamulin, dimetridazole, efrotomycin and valnemulin with MICs ranging from </=0.1 to 1.6 microg/ml. Penicillins, chloramphenicol, tetracyclines, terdecamycin and streptomycin were also active against the isolates. Most isolates were resistant to lincomycin, avilamycin and macrolides (with the exception of terdecamycin).

Animals↗

Nitroimidazoles, Part XXIII--activity of satranidazole series against anaerobic infections.

A large number of nitroimidazoles have been examined for in vitro activity against three anaerobes - Bacteroides fragilis (Bf), a strain of Bf resistant to metronidazole (16a) and Clostridium perfringens and many found to be active. Among these may be mentioned 1-methyl-5-nitroimidazoles carrying N - bound hetetocycles at position 2, such as satranidazole 1a, 1b, 1c, 1k, 1n and 1v which are at least twice as active as metronidazole (16a), ornidazole (16b) and tinidazole (16c). Even more active are 5-nitroimidazolyl benzimidazole 5d, -thiazolidinone 6b and thiadiazolidine dioxide 8a. Many other types of compounds derived from 1-methyl-2-amino-5-nitroimidazole are feebly active. Among 5-nitroimidazoles with a carbon substituent at position 2, 16a, 16b and 16c are equiactive while dimetridazole 14f is more active than 16a against Bf. Some 2-vinyl derivatives are very potent, with 18f and 18i being outstanding. Activity better than that of metronidazole is seen for nitroimidazooxazepines, e.g. 29d. 5-Nitroimidazoles are more active against anaerobes than 4-nitro isomers. Antianaerobic and antiamoebic activities generally run parallel in these classes of compounds. The study has led to the elaboration of the antianaerobic profile of satranidazole 1a.

Amebicides↗

[Amebiasis. Medical treatment. Is there anything better than metronidazole?].

Since 1961, when Cosar pointed out for the first time that metronidazol was a useful pharmacological agent against E. histolytica, several authors have demonstrated its effectiveness against invasive amebiasis in its colonic or extraintestinal variety. The obtained results with metronidazol were so far better compared with the rest of the known amebecides, that in 1974, Elsdon Dew stated that a new era in the medical treatment of the amebiasis had started with the forthcoming use of the agent. However, the frequent and important adverse collateral effects produced in a good number of patients have forced to look for other nitroimidazole derivates, hopefully more efficient and, of course, better tolerated. Thus, the tinidazole, ornidazole, flunidazole, romidazole, ornidazole, flunidazole, dimetridazole, satranidazole, nitrimidazine, panidazole, have been tried and some others are still subject to experimentation, such as the Ro 7-0207 (alpha-chlorometil-2-metil-5-nitro-1-imidazol), the phexinidazole (HOE 239) and the CG 10213-Go from CIBA-Geigy and no significant advantage has been found over the metronidazol. The phexinidazole turned out to be twice as effective as the metronidazole in the experimental hepatic amebiasis of the golden hamster. This fact must be confirmed or discarded in the human hepatic amebiasis.

Amebiasis↗

Diagnosis of Giardia infection in 14 calves.

Fourteen calves, 12 days to 12 weeks old, were treated for diarrhea. Fecal examination for parasitologic, bacteriologic, or viral infection revealed Giardia in all calves; rotavirus and coronavirus were found in some calves. Thirteen affected calves were treated orally with dimetridazole (50 mg/kg of body weight, daily, for 5 days), with complete resolution of the diarrhea and elimination of the Giardia. Giardiasis should be considered as an etiologic agent of diarrhea in calves.

Animals↗

Investigations of toxicity episodes involving chemotherapeutic agents in Victorian poultry and pigeons.

This series of case reports details observations on toxicity episodes in poultry due to a variety of chemotherapeutic agents. These problems arose owing to overdosage, variation in species susceptibility, potentiation of the toxic effects of one substance by the presence of another substance, and particular disease or other on-farm factors. Ignorance and accident were responsible for some of these situations. The episodes involved monensin, salinomycin, nicarbazin, sulphaquinoxaline, dinitolmide, dimetridazole, nitrofurans, streptomycin, and 3-nitro-4-hydroxyphenylarsonic acid.

Animals↗

An outbreak of hexamitiasis in laboratory mice.

Hexamitiasis was encountered in a breeding colony of C(3)H/HeJ mice. The disease was observed in animals under three weeks of age. It was characterized clinically by retarded development, hunched attitude, lethargy, and in some cases by diarrhea and death. Lesions were noted particularly in the duodenum. The intestinal contents were watery and foamy. Histologically, cyst-like formations due to the dilation of the glands of Lieberkühn were seen together with inflammatory reaction in the lamina propria and sloughing of the epithelium. The infection was controlled by the routine administration of dimetridazole in the drinking water.

Animals↗

Experimental spironucleosis (hexamitiasis) in the nude mouse as a model for immunologic and pharmacologic studies.

Experimental infection of the nude (nu/nu) mouse with the intestinal flagellate, Spironucleus (Hexamita) muris, was used as animal model for immunologic studies and for the testing of protozoa cides. The fecal discharge of cysts was shown to correlate with the immune status of the host. It was dependent on the strain, presence of the thymus (nu/nu and nu/+), and age (immunologic maturity). Four protozoacides (dimetridazole, metronidazole, tinidazole, and chlormethoxyacridylamino-diethylaminopropanol-dihydrochloride) were tested in infected mice. All lowered or suppressed the fecal discharge of cysts during treatment; however, the cysts reappeared in the feces when treatment, lasting 1-3 weeks, was terminated. It was concluded that experimental infection of the nude mouse with S muris was an excellent model for immunologic and pharmacologic studies.

Animals↗

Eliminating swine dysentery from selected herds.

In attempts to eliminate swine dysentery from a herd, the total cost of nitroimidazole medication in the water can be estimated at 16/gal over 3-4 weeks and for carbadox in the feed at 70/100 lb over 6-8 weeks. Use of dimetridazole or ipronidazole in the water for 3-4 weeks or carbadox in the feed for 6-8 weeks eliminates Treponema hyodysenteriae from the porcine gut. A 30-day (10 weeks with carbadox) preslaughter withdrawal time should be provided. Impervious surfaces should be thoroughly sanitized, while permeable surfaces and lots should be cleaned, dried and aired well for 2-3 weeks in warm, dry weather and for at least 60 days in cool, damp weather. Animal vectors and fomites must be controlled. Isolation of new breeding stock for 3-4 weeks helps prevent recontamination. While elimination of swine dysentery is not practical in many herds because of poor facilities or lack of producer commitment, a properly designed program can result in economic benefits.

Animals↗