Anorexigenic substances released during infection may hinder the therapeutic efficacy of in-feed antibiotics. Paracetamol (acetaminophen; PARA) inhibits the anorexia of infection and seems to improve the clinical efficacy of doxycycline (DOX) against bacterial respiratory disease in swine herds. In order to verify whether PARA selectively stimulates intake of DOX-medicated feed in diseased pigs, we documented the pharmacokinetics (PK) of DOX when coadministered with PARA and examined the effect of in-feed PARA on the interindividual variability in plasma concentrations after systemic exposure to in-feed DOX in swine herds with respiratory disease. Systemic exposure to DOX was measured with the area under the curve (AUC) of its plasma concentrations over time. First, a rich-sampling PK study of in-feed and i.v. DOX (10 mg/kg of BW) and PARA (30 and 10 mg/kg of BW, respectively) was performed on 5 pigs. The PK profiles of in-feed DOX were used in mathematical simulations to determine 5 optimal sampling times for the farm-based population PK study. A randomized, blind, parallel PK study was performed in 2 herds with bacterial respiratory disease, where liquid feed was fortified with DOX alone (5 mg x kg of BW(-1) x meal(-1)) or combined with PARA (15 mg x kg of BW(-1) x meal(-1)). Medicated meals were given twice, 12 h apart, to group-housed growing pigs (n > 50 pigs x treatment(-1) x herd(-1), totaling 215 pigs). Plasma concentrations of DOX and PARA were measured with HPLC. At variance with our expectations, PARA decreased (P = 0.069) mean AUC of in-feed DOX and did not decrease its variability (P > 0.34). Mean AUC of DOX increased with feed intake and with initial exposure to DOX, and was greater in sick animals. Therefore, symptomatic PARA-induced improvement in bacterial respiratory disease control with DOX is more likely caused by its analgesic/antipyretic effects than by its orexigenic effect. Interindividual variation in the AUC of DOX was large in pigs given group medication, even when sufficient feeding space was allowed and the amount of feed offered was greater than their requirements. Therefore, future studies to improve the efficacy of group antibiotic therapy should focus on feeding behavior characteristics as well as biopharmaceutical properties of medicated feeds.

A multicentre, controlled, randomised and blinded study was carried out in three French pig herds to assess the efficacy of doxycycline administered in the feed for the control of pneumonia. About 20 per cent of 363 pigs from the three fattening units were diseased at the start of the study. Pneumonic lesions were found on pigs examined postmortem and Pasteurella multocida was isolated from the lungs of pigs in all the herds. Mycoplasma hyopneumoniae infection was confirmed either by detection in pneumonic lungs or by seroconversion in pigs sampled three weeks apart. P multocida, Bordetella bronchiseptica and Actinobacillus pleuropneumoniae were isolated from 64 per cent, 50 per cent and 2 per cent, respectively, of 148 nasal swabs. The following variables were significantly different between the treated and untreated groups (P < or = 0.001): the incidence of diseased pigs during the three weeks from the start of treatment (8.1 per cent in treated group v 35.4 per cent in control group), mean daily weight gain over the same period (934 g/day in the treated group v 834 g/day in the control group) and the cure rate of pigs which were diseased at the start of treatment (73.5 per cent in treated group v 35.3 per cent in control group). These data demonstrate that an average dose of 11 mg doxycycline/kg bodyweight per day in feed for eight days was effective in controlling pneumonia due to P multocida and M hyopneumoniae in these fattening pigs.

In a controlled and randomized field trial carried out in three European countries, 219 fattening pigs, from seven farms with respiratory disease problems, were treated intramuscularly for three or five days either with marbofloxacin 2 mg/kg/day, or with amoxicillin 7 mg/kg/day. Pigs were monitored daily until D5 (Day 5) and again at D21, and were weighed at D0 and D21. Pasteurella multocida, Actinobacillus pleuropneumoniae, and Mycoplasma hyopneumoniae were mainly identified in the pig lungs. The difference in the cure rate (74.5% in marbofloxacin group versus 68% in the amoxicillin group) was not significant. Mean rectal temperature was significantly lower after treatment with marbofloxacin. Other criteria tended to be favourable for the marbofloxacin group, although differences were not significant. The time to cure tended to be shorter for the marbofloxacin group (24.3% of pigs at 24 hours post-treatment versus 12.1% in the amoxicillin group). Marbofloxacin and amoxicillin relapse rates were 11.9% and 17.2% respectively (not significant) and daily weight gain was 746 g in the marbofloxacin group versus 687 g in the amoxicillin group (not significant). The 2% marbofloxacin solution was significantly better tolerated than amoxicillin.

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