Pharmacokinetics of Sulfadimethoxine and Sulfamethoxazole in Combination with Trimethoprim after Oral Single- and Multiple-Dose Administration to Healthy Pigs

The pharmacokinetics were studied of sulfadimethoxine (SDM) or sulfamethoxazole (SMX) in combination with trimethoprim (TMP) administered as a single oral dose (25 mg + 5 mg per kg body weight) to two groups of 6 healthy pigs. The elimination half-lives of SMX and TMP were quite similar (2–3 h); SDM had a relatively long half-life of 13 h. Both sulfonamides (S) were exclusively metabolized to N4-acetyl derivatives but to different extents. The main metabolic pathway for TMP was O-demethylation and subsequent conjugation. In addition, the plasma concentrations of these drugs and their main metabolites after medication with different in-feed concentrations were determined. The drug (S:TMP) concentrations in the feed were 250:50, 500:100, and 1000:200 mg per kg. Steady-state concentrations were achieved within 48 h of feed medication, twice daily (SDM+TMP) or three times a day (SMX+TMP). Protein binding of SDM and its metabolite was high (>93%), whereas SMX, TMP and their metabolites showed moderate binding (48–75%). Feed medication with 500 ppm sulfonamide combined with 100 ppm TMP provided minimum steady-state plasma concentrations (C _ss,min) higher than the concentration required for inhibition of the growth of 90% of Actinobacillus pleuropneumoniae strains (n = 20).     

Pharmacokinetics of sulfadimethoxine and sulfamethoxazole in combination with trimethoprim after intravenous administration to healthy and pneumonic pigs

The pharmacokinetics of two sulfonamide/trimethoprim combinations were investigated after intravenous administration to clinically healthy pigs and to the same pigs following a challenge with Actinobacillus pleuropneumoniae toxins. Endobronchial challenge with A.pleuropneumoniae toxins resulted in fever, increased white blood cell counts and decreased water and feed consumption. Healthy, as well as febrile, pigs were given sulfadimethoxine (SDM) or sulfamethoxazole (SMX) intravenously at a dose of 25 mg/kg b.w. in combination with 5 mg trimethoprim (TMP) per kg body weight. The pharmacokinetic parameters of the sulfonamides as well as their main metabolites (acetyl sulfonamides) were not significantly different in healthy and febrile pigs. In healthy and pneumonic pigs, the mean elimination half-lives of SDM were 12.9 h and 13.4 h, respectively, those of SMX 2.5 h and 2.7 h, respectively, and those of TMP 2.8 h and 2.6 h, respectively. Distribution volumes in healthy and febrile pigs of SDM and SMX varied between 0.2 and 0.4 L/kg, and those of TMP between 1.1 and 1.6 L/kg. The mean AUC of TMP was decreased and the volume of distribution and total body clearance of TMP were increased in febrile pigs. Protein binding of the drugs and metabolites studied were not significantly changed after toxin-induced fever. The extent of protein binding of SDM, SMX and TMP was in the range 94–99%, 45–56% and 40–50%, respectively. Based on knowledge of in vitro antimicrobial activity of the drug combinations against A.pleuropneumoniae it was concluded that after intravenous administration of the dose administered (30 mg/kg of the combination preparations) to healthy and pneumonic pigs, plasma concentrations of SMX and TMP were above the concentration required for growth inhibition of 50% of A., pleuropneumoniae strains for approximately 16 h, whereas bacteriostatic plasma concentrations of SDM were still present after TMP had been eliminated from plasma. Because of similar elimination half-lives of SMX and TMP in pigs this combination is preferred to the combination of SDM with TMP.     

In vitro susceptibility of some porcine respiratory tract pathogens to aditoprim, trimethoprim, sulfadimethoxine, sulfamethoxazole, and combinations of these agents

The in vitro antimicrobial activities of aditoprim (AP), a new dihydrofolate reductase (DHFR) inhibitor, trimethoprim (TMP), sulfadimethoxine (SDM), sulfamethoxazole (SMX), and combinations of these drugs against some porcine respiratory tract pathogens were determined by use of an agar dilution method. The minimal inhibitory concentrations (MIC) of these agents were determined twice against Bordetella bronchiseptica (n = 10), Pasteurella multocida (n = 10), and Actinobacillus pleuropneumoniae (n = 20) strains isolated from pigs suffering from atrophic rhinitis or pleuropneumonia. All B bronchiseptica strains were resistant to AP and TMP. The MIC50 values of AP and TMP for P multocida were 0.25 and 0.06 microgram/ml, respectively, and for A pleuropneumoniae, 1 and 0.25 microgram/ml, respectively. The MIC50 values of SDM and SMX for B bronchiseptica were 4 and 1 micrograms/ml, respectively; for P multocida, 16 and 8 micrograms/ml, respectively; and for A pleuropneumoniae, 16 and 8 micrograms/ml, respectively. The investigated combinations of the DHFR inhibitors and the selected sulfonamides had synergism for the A pleuropneumoniae strains; the MIC90 values of the combinations were less than or equal to 0.06 microgram/ml. Potentiation was not observed for the B bronchiseptica and the P multocida isolates. The MIC of the combinations against B bronchiseptica and P multocida corresponded respectively to the concentrations of the sulfonamides and the DHFR inhibitors in the combinations. For A pleuropneumoniae, 2 types of strains were used (25% of serotype 2 and 75% of serotype 9). Type-2 strains had lower susceptibility than type-9 strains to AP and TMP as well as to SDM and SMX (at least a fourfold difference in MIC between the 2 types of strains).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effectiveness of doxycycline in the prevention of an experimental infection with Actinobacillus pleuropneumoniae in pigs

The effectiveness of medication with doxycycline in feed in the control of pleuropneumonia in pigs was tested using an Actinobacillus pleuropneumoniae serotype 1 aerosol challenge model. Two groups of 10 animals were used for the challenge, a 'medicated group' and an 'unmedicated group'. A third group of four animals was used as a 'control group'. Pigs from the medicated group were provided with feed containing 250 p.p.m. doxycycline (HIPRAMIX/DOXI) for 8 consecutive days and were challenged on the fifth day of treatment. No clinical signs were observed in pigs from the 'control group'. Four animals from the 'unmedicated group' died within the first 48 h after challenge with clinical and lesional evidence of an acute form of pleuropneumonia. Clinical signs of animals surviving the first 48 h were progressively less severe and showed lesions similar to those described for subacute-chronic forms of the disease. However, only one animal from the 'medicated group' showed clinical signs of a chronic form of pleuropneumonia. Reisolation of A. pleuropneumoniae was more evident from lung tissues of animals fed the doxycycline-free feed (70%), coinciding with the presence of both acute and subacute lesions. However, the micro-organism could be reisolated from only one animal which belonged to the 'medicated group'. It is concluded that the treatment of pigs with 250 p.p.m. doxycycline (HIPRAMIX/DOXI) prevents disease caused by A. pleuropneumoniae.     

Effects of ketoprofen and flunixin in pigs experimentally infected with Actinobacillus pleuropneumoniae

The antipyretic effect of the non-steroidal anti-inflammatory drugs (NSAIDs) ketoprofen (3 mg/kg) and flunixin (2 mg/kg) were studied in pigs. The drugs were administered intramuscularly at 8 and 32 h following endobronchial challenge with Actinobucillus pleuropneumoniae. Infected (non-medicated) and non-infected (non-medicated) controls were used. Endobronchial challenge with Actinobucillus pleuropneumoniae induced laboured breathing, coughing, fever, reduced food and water consumption and increased white blood cell counts. At autopsy, pleuropneumonia was evident. Ketoprofen showed a highly significant antipyretic effect but flunixin did not. The decrease in food consumption of ketoprofen-treated pigs was significantly less than that of the infected (non-medicated) controls. Blood parameters were not significantly influenced by either NSAID and, at necropsy, gastric and renal side-effects were not observed for either drug.     

Comparison of conventional and long-acting oxytetracyclines in prevention of induced Actinobacillus (Haemophilus) pleuropneumoniae infection of growing swine.

These experiments tested the hypothesis that long-acting oxytetracycline (oxytetracycline-LA) was more effective than regular oxytetracycline in preventing porcine pleuropneumonia when administered either 24 or 48 h prior to experimental challenge with virulent strains of Actinobacillus pleuropneumoniae. Two experiments (1 and 2) were conducted using growing pigs (average weight 12-15 kg). Antibiotic treatments were administered once intramuscularly at 20 mg/kg body weight; controls received an equivalent volume of saline. Clinical signs were recorded over seven days, and mortality rates and pathological lesions were analyzed using analysis of variance. Serum oxytetracycline levels were compared 48 and 72 h postinjection. All pigs developed clinical disease following experimental infection. Actinobacillus pleuropneumoniae was recovered from 42% of experiment 1 pigs and all of experiment 2 pigs. The data showed that both oxytetracycline and oxytetracycline-LA given at the same dose protected pigs against experimental infection when given 24 h prior to challenge, and there was no difference between the efficacy of the two drugs in this experiment. When administered 48 h prior to challenge, only oxytetracycline-LA reduced the clinical signs and pathological changes following A. pleuropneumoniae challenge. Between 48 and 72 h postinjection, oxytetracycline-LA blood levels were significantly greater compared to oxytetracycline-treated pigs.     

Experimental infections with Actinobacillus pleuropneumoniae in pigs--II. Comparison of antibiotics for oral strategic treatment.

The present study was aimed at scrutinizing the efficacy of oral antimicrobial treatments at experimental challenge using a strain of Actinobacillus pleuropneumoniae serotype 2 known to cause severe disease. SPF pigs aged 10 weeks were infected intranasally and the antimicrobial treatments were initiated 5 h prior to that exposure. Several antimicrobial drugs, as well as the length of the treatment period, were elucidated. The outcome of the challenge was monitored by registration of clinical symptoms, weight gains and the development of serum antibodies to A. pleuropneumoniae. At necropsy, the magnitude of pathological lesions in the respiratory tract and the rate of reisolation of the infective strain were recorded. Animals that became diseased displayed a decreased growth rate caused, to a large extent, by a reduced feed intake. The performance with respect to daily weight gain and feed conversion corresponded well with the clinical signs developed and serologic reactions, as well as with the findings made at necropsy. The results obtained among pigs treated with enrofloxacin, but also with florfenicol or chlortetracycline, were superior to those of pigs treated with penicillin, tiamulin or tilmicosin. A positive effect was obtained using a strategic in-feed medication against infection with A. pleuropneumoniae. Provided that the drug used is effective against the target microbe, initiating treatment prior to infection appeared to be more important than the length of the treatment. It should, however, be remembered that A. pleuropneumoniae was reisolated from all but one medicated group following an experimental challenge given after initiating the medication. Consequently medical treatment as described did not eradicate the microbe.     

3-Acetyl-4'-isovaleryl tylosin for prevention of swine dysentery

The 21 field isolates of Treponema hyodysenteriae which were tested were sensitive to 3-acetyl-4'-isovaleryl tylosin (AIV); the minimal inhibitory concentration was 0.25 to 16 micrograms/ml. 3-Acetyl-4'-isovaleryl tylosin administered prophylactically to pigs at concentrations of 5 to 100 mg/kg of feed and tylosin at 110 mg/kg of feed for 28 or 31 days prevented swine dysentery induced by tylosin-sensitive T hyodysenteriae strain SQ2; 15 nonmedicated, inoculated control pigs had bloody diarrhea, and 9 pigs died. In 2 additional trials, AIV administered prophylactically for 28 days at 55 or 110 mg/kg of feed prevented swine dysentery induced by tylosin-insensitive T hyodysenteriae strain B204. All of the inoculated principal pigs medicated with AIV at 55 or 110 mg/kg of feed or carbadox at 55 mg/kg of feed and the noninoculated sentinel pigs for each group had solid feces throughout the 56-day trial. In the nonmedicated, inoculated control groups, bloody diarrhea began at 4 to 5 days after inoculation was done, and 9 of 10 principal pigs and 6 of 9 sentinel pigs had dysentery; 2 pigs died. In the groups medicated with AIV at 27.5 or 5.5 mg/kg of feed, all 5 principal pigs and 3 or 4 sentinel pigs in each group had dysentery; 3 or 4 pigs in each group died. In the group medicated with tylosin at 110 mg/kg of feed, 7 of 10 principal pigs and all 9 sentinel pigs had dysentery; 1 pig died.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of efrotomycin in feed on the quantity, duration, and prevalence of shedding and antibacterial susceptibility of Salmonella typhimurium in experimentally infected swine

The influence of efrotomycin administered at the rate of 16 mg/kg of feed in 10 Salmonella typhimurium-inoculated pigs was determined by comparing this group with a group of 10 pigs inoculated with S typhimurium that were given nonmedicated feed. Two control groups of 4 noninoculated pigs each, 1 group medicated with efrotomycin at 16 mg/kg of feed, the other nonmedicated, also were evaluated. An inoculum of 1.7 x 10(10) colony-forming-units/pig induced colonization of S typhimurium in all 20 pigs. Evaluation of the quantity of shedding did not reveal a clear or consistent treatment-related increase in S typhimurium counts; mean differences between the nonmedicated and medicated groups never exceeded 1 log unit. On the last day of the study (day 56 of the medication), 8 nonmedicated and 9 medicated pigs were determined to be infected with S typhimurium via enrichment procedures, so there was no difference in duration of shedding, and there were no significant differences in prevalence of shedding between the nonmedicated and medicated groups at any of the sampling times. Of 1,340 S typhimurium colonies isolated from the nonmedicated and medicated groups, 1,330 were susceptible to all 12 antibacterials tested, indicating no treatment-related effect on susceptibility. At necropsy, S typhimurium was not isolated from any liver or spleen specimens, and was isolated from only 2 of 20 lymph nodes. However, S typhimurium was isolated via enrichment from the cecal contents from all 20 pigs. There were no treatment-related differences in feed consumption, weight gain, or feed efficiency. Appreciable differences in the measurements were not found between the efrotomycin-medicated and nonmedicated pigs.     

Field studies with in‐feed medication of pigs in the Netherlands using the anthelmintic thiophanate with particular reference to efficacy against Ascaris suum

Summary

Studies on the efficacy in pigs of low level in‐feed medication with the anthelmintic thiophanate at a minimum intake of 6 mg/kg/day for fourteen days are reported. A trial was conducted to compare a group of medicated fattening pigs with a similar unmedicated group on premises known to have a high challenge of Ascaris spp. Daily growth rate was improved whilst feed conversion ratio and the liver condemnation rate were reduced in the treatment group.

Routine medication of a whole herd using this regime contributed to a great improvement of the herd production when assessed by the above criteria. User studies in various geographical areas of the Netherlands involving 1500 adult pigs and 1200 fattening pigs medicated with thiophanate in‐feed for fourteen days demonstrated that the compound eliminated the faecal worm egg output and was readily accepted and tolerated by pigs.     

Spray-dried plasma improves growth performance and reduces inflammatory status of weaned pigs challenged with enterotoxigenic Escherichia coli K88

We investigated whether spray-dried plasma (SDP) improved growth and health of piglets challenged with enterotoxigenic Escherichia coli K88 (ETEC). Forty-eight pigs weaned at 21 d (BW = 4.88 +/- 0.43 kg) received one of four diets containing 6% SDP or fish proteins (as-fed basis) either nonmedicated (SDP-NM and FP-NM diets) or medicated with 0 or 250 mg/kg of colistine + 500 mg/kg of amoxycycline (SDP-M and FP-M diets), for 15 d. On d 4, pigs were orally challenged with ETEC. On d 15, eight pigs per dietary group were killed, blood and saliva were collected for analysis of K88 fimbriae-specific immunoglobulin (Ig)-A, and jejunum was removed for villi preparation, histological analysis, and cytokine expression. The presence or absence of K88 receptors (K88+ and K88- pigs respectively) was determined by villous adhesion assay. Effects of protein source on ADG (P = 0.04) and ADFI (P < 0.01), as well of medication on ADFI (P < 0.02), of all pigs were observed. In sacrified pigs, there was an effect of protein source on ADG (P = 0.03) and ADFI (P < 0.001), as well an interaction between medication and presence of K88 receptor (P = 0.02) for feed:gain ratio. Plasma K88 specific IgA were low in all K88 pigs and higher in K88+ pigs fed FP-NM compared with all the other groups (P < 0.05), except SDP-M. An interaction was found among protein source, medication, and presence of K88 receptors (P = 0.04). Saliva IgA concentrations were high in all pigs fed FP-NM and low in all other pigs. Jejunum of pigs fed FP-NM showed some ulcerations, edema, and mild inflammatory cell infiltration (ICI). In pigs fed FP-M, edema was reduced. Conversely, only a mild ICI was observed in pigs fed SDP-NM and SDP-M. Crypt depth was increased in K88+ pigs fed SDP-NM and an interaction between protein source and presence of K88 receptors was observed (P < 0.05). Expressions of tumor necrosis factor-alpha and interleukin (IL)-8 were lower in pigs fed SDP-NM and SDP-M than in those fed FP-NM and FP-M, either K88- or K88+ (P < 0.01). In pigs fed FP diets, expression of IL-8 tended to increase (P = 0.08) in K88+ compared with K88- subjects. Expression of interferon-gamma increased in K88 and K88+ pigs fed FP-M as compared with other pigs (P < 0.01). These results indicate that feeding with SDP improved growth performance and protected against E. coli-induced inflammatory status, and suggest that use of SDP-NM can be considered a valid antibiotic alternative.     

The effect of continuous in-feed medication with thiophanate on Ascaris suum and Oesophagostomum spp. egg output in young pigs

The full potential of anthelmintics now available for single dose treatment is not achieved because the devising system for worm control in piglets/weaners is not efficiently applicable in practice. Therefore an in-feed medication programme for growing young pigs, allowing only one feed lot to be handled by the farmer, was tested in two studies. Study A Feed containing 0.0225% thiophanate was continuously fed almost ad lib. to piglets from birth right up to about 25 kg body weight when ready for fattening. This control measure effectively prevented A. suum and Oesophagostomum from becoming established during the whole pre-fattening period, thus allowing "worm-free" weaners to be produced. -33% of animals receiving unmedicated feed harboured mature Oesophagostomum already at an age of 63 days when first examined. Three out of 97 unmedicated pigs were then A. suum egg-count positive. At the same time all medicated pigs, except one with a low Oesophagostomum egg output, were egg-count negative. All medicated were still egg-count negative at 23-29 days after the withdrawal of the feed. About 30% of unmedicated pigs were then shedding eggs of A. suum and Oesophagostomum respectively. At 45-49 days after the withdrawal of the medicated feed 8% of previously medicated pigs and 43% of unmedicated pigs were A. suum egg-count positive. The corresponding figures for Oesophagostomum egg-count positive pigs were 6% and 40% respectively. The acquisition of worm infections by previously medicated pigs most probably was made in the fattening unit after the withdrawal of the thiophanate medicated feed. Study B In this study it was further substantiated that in-feed medication of pigs with thiophanate prevents A. suum from becoming established. All treated pigs were A. suum egg-count negative at Day 43 and 46 after the withdrawal of the medicated feed whereas about 62% of untreated control pigs were shedding A. suum eggs at the same time. This finding justify the proposal that the in-feed medication performed prevented larval migration. Furthermore it was shown that the in-feed medication must proceed right up to the transfer of piglets to the fattening unit in order to achieve its full potential. Farrowing pens may be heavily contaminated with infective Oesophagostomum larvae at the end of the pre-fattening period resulting in sudden and heavy nodular worm infections after the withdrawal of the medicated feed.     

Effects of a Quillaja saponaria extract on growth performance and immune function of weanling pigs challenged with Salmonella typhimurium

Ninety-six pigs (initially 8.9 kg and 24 d of age) were used in a 28-d experiment to determine the effects of Quillaja saponaria extract (QS) on weanling pig growth performance and immune function in response to enteric disease challenge with Salmonella typhimurium (ST). Experimental treatments were arranged in a 2 x 4 factorial with main effects of disease challenge (control vs ST-challenge) and dietary addition of QS (0, 125, 250, or 500 mg/kg). Pigs were fed QS diets for 14 d and then challenged orally with ST or sterile media. There were no differences in ADG or ADFI among dietary treatments, but gain/feed ratio (G/ F) was depressed (P < 0.06) in pigs fed 250 mg/kg QS. ST-challenge reduced ADG (P < 0.05), ADFI (P < 0.05), and G/F (P < 0.05) 1 wk after challenge. Daily estimates revealed reductions in feed intake in ST-infected pigs on d 2 to 5 following infection (P < 0.05), and rectal temperature was increased maximally 2 d following infection (P < 0.05). There was a marked decline in serum IGF-I during the 6 d after ST-infection (P < 0.05). ST-challenge produced a rise (P < 0.05) in serum haptoglobin on d 7 after challenge, and serum alpha1-acid glycoprotein (AGP) in ST-challenged pigs also was elevated (P < 0.05) above controls on d 7 and 14 after challenge. Serum immunoglobulin (Ig) M increased (P < 0.05) over time in both groups, and serum IgM of ST-challenged pigs was greater than controls on d 7 after challenge (P < 0.05). Serum IgG was not affected by enteric disease challenge; however, on d 7 and 14 after disease challenge, serum IgG for both groups was greater (P < 0.05) than on d 0. Dietary QS had no significant influence on any of the end points used to characterize the acute phase response to ST-challenge. Phagocytic cell function was depressed in pigs fed 250 (P < 0.05) and 500 (P < 0.05) mg/kg as compared to pigs fed 125 mg/kg QS. Yet, there was no difference in phagocytic function among pigs fed 0, 250, or 500 mg/kg QS. We conclude that this model of enteric disease invokes an acute phase response accompanied by decreases in feed intake and serum IGF-I. Furthermore, dietary QS, at the levels fed in this study, appears to offer little benefit to growth performance or immune function in the presence or absence of ST-challenge.     

Assessment of the efficacy of tilmicosin phosphate to eliminate Actinobacillus pleuropneumoniae from carrier pigs

The aim of this study was to evaluate the efficacy of in-feed medication with tilmicosin phosphate in order to eliminate or reduce the carriage of Actinobacillus pleuropneumoniae in the tonsils of carrier pigs. Two groups of 6 carrier animals received either a non-medicated feed (control group) or feed medicated with 400 ppm of tilmicosin phosphate (treated group) for 30 d. Three sentinel pigs were then introduced in each group and left for 29 d. The presence of A. pleuropneumoniae in tonsils was monitored using several techniques, including polymerase chain reaction (PCR). At the end of the treatment all of the control animals, but only 1 treated pig, were positive by PCR from tonsillar surface material. However, at necropsy, all control and most treated animals, as well as 1 sentinel animal, in both groups were positive by PCR from whole tonsils. In conclusion, under the experimental conditions, in-feed treatment with 400 ppm of tilmicosin phosphate significantly reduced the presence of A. pleuropneumoniae on the surface of tonsils but was unable to completely eliminate the organism from deeper tonsillar tissues and to prevent bacterial shedding by carrier animals.     

Streptococcal meningitis in pigs: field trial to study the prophylactic effect of trimethoprim/sulphadiazine medication in feed

Half the progeny in a 200-sow herd (2045 pigs) was given feed medicated with 500 g/tonne of a 1:5 trimethoprim/sulphadiazine mixture from three to nine weeks of age. The other half (1989) acted as controls. The trial lasted 12 months. No difference was observed between the two groups in the incidence of streptococcal meningitis and the morbidity and mortality from all disease causes during the growing/fattening periods did not differ significantly. The main diseases encountered were pneumonia (7.24 per cent), streptococcal meningitis (5.12 per cent), leg and foot disorders (3.34 per cent) and the after-effects of vices (1.86 per cent). The resistance of faecal coliforms to trimethoprim was studied during the six-week period of trimethoprim/sulphadiazine feeding. Faecal coliforms in both medicated and non-medicated groups developed almost 100 per cent resistance. However, resistance developed more slowly in the untreated pigs. The medicated pigs showed a small overall improvement in feed conversion rate up to 18 weeks of age mainly because of a marked improvement between three and six weeks.     

Effect of fenbendazole and pyrantel tartrate on the induction of protective immunity in pigs naturally or experimentally infected with Ascaris suum

An experiment was conducted with 96 weanling pigs (avg initial wt 18.5 kg) divided into six treatment with two replicates of eight pigs each. Pigs in Treatments 1, 2 and 3 were penned in outside pens with dirt lots that previously were contaminated with A. suum ova to induce a natural ascaris infection. Pigs in Treatments 4, 5 and 6 were penned in an open-front building with solid concrete floors and were experimentally infected with 2,000 embryonated A. suum. ova on d 1, 15 and 29 of the experiment. Pigs in Treatments 1 and 4 were medicated with fenbendazole (FBZ, 3 mg/[kg BW.d]) for three consecutive days during three consecutive time periods. Pigs in Treatments 2 and 5 were medicated with pyrantel tartrate (PT, 106 mg/kg feed) for 28 d. Pigs in Treatments 3 and 6 served as infected, unmedicated controls. All pigs were challenged with 100 A. suum eggs 7 d after termination of the final FBZ treatment. All pigs were killed 66 d after challenge and worms were recovered. Fenbendazole treatment resulted in greater (P less than .07) average daily gain than PT treatment in pigs penned outside. Among inside pigs, FBZ treatment resulted in better (P less than .02) feed utilization than in controls. The FBZ and PT treatments reduced (P less than .03) the total number of A. suum, the length and weight of female ascarids and the length of male ascarids compared with controls. A natural continual infection with A. suum was less effective than experimental infection in inducing protective immunity in pigs.     

Blood gas stability and hematological changes in experimentally-induced acute porcine pleuropneumonia.

Blood gas and hematological responses to acute, mild Actinobacillus pleuropneumoniae infection of growing pigs was studied. Six pigs (average weight 10.1 kg) were experimentally infected intranasally with A. pleuropneumoniae serotype 5. Four pigs served as controls. Rectal temperatures and arterial blood for gas analysis and hematology were taken at 0, 8, 16, 24, 48 and 72 h postinfection. All infected pigs became febrile showing clinical signs typical of mild to moderate porcine pleuropneumonia; controls remained asymptomatic. Neutrophilia with bands and lymphopenia were observed only in infected pigs. Arterial partial pressures of O2 and CO2, and pH did not change in infected pigs. All pigs were killed after 72 h, and lungs were examined and cultured. Gross and microscopic lesions consistent with porcine pleuropneumonia were seen in 3/6 and 5/6 infected lungs, respectively. Control lungs were grossly normal with no histological evidence of pleuropneumonia. We conclude that in mild, acute porcine pleuropneumonia as established experimentally, a leukogram typical of acute inflammation and stress is seen; however, hypoxemia and alveolar hypoventilation are not features of this form of the disease.     

Pleuropneumonia caused by Actinobacillus pleuropneumoniae biotype 2 in growing and finishing pigs.

Actinobacillus pleuropneumoniae biotype 2 was isolated in pure culture or as the predominant isolate from the lungs of 9 growing and finishing pigs with pleuropneumonia. Gross and microscopic lesions resembled those caused by A. pleuropneumoniae biotype 1 serotypes (Nos. 1, 5, and 7) traditionally seen in the United States. The overall mortality rate for growing and finishing pigs on this 1,200-sow farrow-to-finish farm ranged from 0.37% to 0.84% per month from July 1990 to February 1991, and mortality due to respiratory disease ranged from 0.17% to 0.52% per month for the same period. This Actinobacillus species did not require V factor (no satellitism on blood agar with a Staphylococcus streak), was strongly beta-hemolytic, and demonstrated restriction fragment length polymorphisms in hybridization studies with A. suis, A. lignieresii, and A. equuli. Biochemically, the isolate most closely resembled A. pleuropneumoniae, and a DNA fragment considered specific for A. pleuropneumoniae biotypes 1 and 2 was demonstrated using polymerase chain reaction. Necrohemorrhagic pleuropneumonia similar to that caused by A. pleuropneumoniae biotype 1 was reproduced experimentally in 2 4-week-old pigs inoculated intratracheally with broth cultures of the A. pleuropneumoniae biotype 2. This study demonstrated the presence of A. pleuropneumoniae biotype 2 in the United States.     

The synergistic activity of tiamulin and chlortetracycline: in-feed treatment of bacterially complicated enzootic pneumonia in fattening pigs

The antibacterial effects of a combination of tiamulin and chlortetracycline in vitro against a number of field isolates of Pasteurella multocida, Haemophilus pleuropneumoniae and Bordetella bronchiseptica were examined. There was a marked synergism between the two antibiotics against all eight isolates of P multocida, against seven of nine isolates of H pleuropneumoniae and against the single strain of B bronchiseptica tested. Two field trials were carried out on a herd with a history of complicated enzootic pneumonia where the presence of Mycoplasma hyopneumoniae and P multocida had been established and subsequently the presence of H pleuropneumoniae was discovered. Feed containing tiamulin at 100 ppm combined with chlortetracycline at 300 ppm was given for seven days to pigs affected with pneumonia, and the results were compared with untreated controls and pigs receiving chlortetracycline at 300 ppm. There was a follow-up observation period of three weeks when all groups received unmedicated feed. During the medication period the combination treated groups showed a statistically significant increase in average daily weight gain of 156 g (20.4 per cent) and in feed conversion efficiency of 0.576 (20.8 per cent) and a numerical improvement in average disease score in comparison with the untreated controls. These improvements were approximately double those observed in the groups treated with 300 ppm chlortetracycline which showed improvements of 93 g (12.2 per cent) in average daily gain and 0.301 (10.9 per cent) in feed conversion efficiency. During the following three weeks most of the initial gains were lost, probably owing to the reinfection of the treated groups by the untreated controls.     

Pharmacokinetics and bioavailability of trimethoprim-sulfamethoxazole in alpacas

The pharmacokinetics and bioavailability of trimethoprim-sulfamethoxazole (TMP-SMX) were studied in six healthy male-castrate alpacas (Lama pacos) after intravenous (i.v.) or oral (p.o.) drug administration of 15 mg/kg TMP-SMX using a crossover design with a 2-week washout period. After 90 days one group (n = 3) was given a p.o. dose of 30 mg/kg TMP-SMX and the other group (n = 3) was given a p.o. dose of 60 mg/kg TMP-SMX. After i.v. administration of 15 mg/kg of TMP-SMX the mean initial plasma concentration (C0) was 10.75 +/- 2.12 microg/mL for trimethoprim (TMP) and 158.3 +/- 189.3 microg/mL for sulfamethoxazole (SMX). Elimination half-lives were 0.74 +/- 0.1 h for TMP and 2.2 +/- 0.6 h for SMX. The mean residence times were 1.45 +/- 0.72 h for TMP and 2.8 +/- 0.6 h for SMX. The areas under the respective concentration vs. time curves (AUC) were 2.49 +/- 1.62 microg h/mL for TMP and 124 +/- 60 microg h/mL for SMX. Total clearance (Clt) for TMP was 21.63 +/- 9.85 and 1.90 +/- 0.77 mL/min kg for SMX. The volume of distribution at steady state was 2.32 +/- 1.15 L/kg for TMP and 0.35 +/- 0.09 L/kg for SMX. After intragastric administration of 15, 30 and 60 mg/kg the peak concentration (Cmax) of SMX were 1.9 +/- 0.8, 2.6 +/- 0.4 and 2.8 +/- 0.7 microg/mL, respectively. The AUC was 9.1 +/- 5, 25.9 +/- 3.3 and 39.1 +/- 4.1 microg h/mL, respectively. Based upon these AUC values and correcting for dose, the respective bioavailabilities were 7.7, 10.5 and 7.94%. Trimethoprim was not detected in plasma after intragastric administration. These data demonstrate that therapeutic concentrations of TMP-SMX are not achieved after p.o. administration to alpacas.