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The objectives of this study were to compare the plasma and lung tissue pharmacokinetics of tilmicosin in healthy and Mycoplasma gallisepticum-infected chickens. Tilmicosin was orally administered at 4, 7.5 and 10 mg/kg body weight (b.w) for the infected and 7.5 mg/kg b.w for the uninfected control group. We found no significant differences in plasma tilmicosin pharmacokinetics between diseased and healthy control chickens. In contrast, the lung tissues in M. gallisepticum-infected chickens displayed a t 1/2 (elimination half-life) 1.76 times longer than for healthy chickens. The C max (the maximum concentration of drug in samples) of tilmicosin in M. gallisepticum-infected chickens was lower than for controls at 7.5 mg/kg b.w (p < .05), and the AUC inf (the area under the concentration-time curve from time 0 extrapolated to infinity) in infected chickens was higher than for the healthy chickens (p < .05). The mean residence time of tilmicosin in infected chickens was also higher than the healthy chickens. These results indicated that the lungs of healthy chickens had greater absorption of tilmicosin than the infected chickens, and the rate of elimination of tilmicosin from infected lungs was slower., (© 2020 John Wiley & Sons Ltd.)

The study was carried out under field conditions in a commercial farm, and 1,440 as-hatched Ross-308 broilers were included. Broilers were randomly distributed into 24 experimental 4-m(2) pens (60 broilers/pen). Pens were randomized to the 3 treatment groups: a) tylvalosin 10 mg/kg of live BW during 2 d, b) positive control (tylosin during 2 d), and c) negative control (no treatment). The drugs were provided in the water supply. Mortality, individual BW, and feed intake were assessed. Clostridium presence was assessed in fecal and cecal samples, coccidian oocyst counts were assessed in fecal samples, and bacterial diversity was assessed in ileal content. Live BW at 42 d old was significantly better in the tylvalosin group than in tylosin and no-treatment groups, with tylvalosin-treated broilers reaching 80 to 100 g higher final live weight. Average daily gain results mirrored BW findings. The improvement of feed conversion rate with tylvalosin amounted to 0.13 and to 0.10 versus tylosin and no-treatment, respectively, with mortality being similar in all groups. Significantly reduced sulfite-reducing Clostridium and Clostridium perfringens counts in tylvalosin and tylosin groups versus the no-treatment group were observed in cecum content samples. In conclusion, according to the present study results, tylvalosin, at doses substantially lower than registered for poultry in Europe, has proven effective in controlling the colonization of the cecum by Clostridium ssp. in broilers, improving some productive performances.

The use of antimicrobials in production animals has become a worldwide concern in the face of rising resistance levels in commensal, pathogenic and zoonotic bacteria. In the years 2007 and 2008 antimicrobial consumption records were collected during two non consecutive production cycles in 32 randomly selected Belgian broiler farms. Antimicrobials were used in 48 of the 64 monitored production cycles, 7 farms did not use any antimicrobials in both production cycles, 2 farms only administered antimicrobials in one of the two production cycles, the other 23 farms applied antimicrobial treatment in both production cycles. For the quantification of antimicrobial drug use, the treatment incidences (TI) based on the defined daily doses (the dose as it should be applied: DDD) and used daily doses (the actual dose applied: UDD) were calculated. A mean antimicrobial treatment incidence per 1000 animals of 131.8 (standard deviation 126.8) animals treated daily with one DDD and 121.4 (SD 106.7) animals treated daily with one UDD was found. The most frequently used compounds were amoxicillin, tylosin and trimethoprim-sulphonamide with a mean TI(UDD) of 37.9, 34.8, and 21.7, respectively. The ratio of the UDD/DDD gives an estimate on correctness of dosing. Tylosin was underdosed in most of the administrations whereas amoxicillin and trimethoprim-sulphonamide were slightly overdosed in the average flock., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Infectious sinusitis, a common condition seen in adult pheasants, is primarily caused by Mycoplasma gallisepticum. The aims of the present study were to investigate the pathogenicity of M. gallisepticum in 14-day-old pheasants and evaluate the macrolide antibiotic tylvalosin (TVN) as a treatment for infectious sinusitis. The minimum inhibitory concentration of TVN for five isolates of M. gallisepticum taken from pheasants confirmed their susceptibility to TVN (range: 0.002 to 0.008 µg/ml). One of the isolates (G87/02) was inoculated intranasally into 72 pheasants (two groups of 36) at 14 days of age. Eight days later, when 18/72 (25%) of the pheasants showed clinical signs, one group was treated with 25 mg TVN/kg bodyweight daily in drinking water for three consecutive days. An uninfected, unmedicated control group (n=12) was also included. In contrast to the uninfected control group, a range of clinical signs typical of infectious sinusitis with varying severity was observed in challenged birds and M. gallisepticum was re-isolated from the infraorbital sinus and the eye/conjunctiva at necropsy, 22 days post challenge. In comparison with untreated birds, medication with TVN significantly reduced clinical signs and the re-isolation/detection of M. gallisepticum (P≤0.0021). The daily liveweight gain of treated birds was significantly increased in comparison with untreated birds (P=0.0002), and similar to daily liveweight gains observed in the uninfected control group. In conclusion, TVN at 25 mg/kg bodyweight daily for three consecutive days in drinking water was efficacious in the treatment of M. gallisepticum infection induced by challenging 14-day-old pheasants.

Ten-to-14-day-old replacement chickens were vaccinated subcutaneously in the neck with a Mycoplasma gallisepticum bacterin. A few days later, 40% of the flock developed cellulitis of the head. Birds were submitted for diagnostic investigation between 4 and 6 wk of age. Histology revealed lesions in the subcutis consistent with oil-emulsified vaccine/bacterin reaction. No significant bacteria were isolated from the lesions. Birds were treated with 1 mg of methyl prednisol acetate intramuscularly. Improvement was noted as early as 12 hr posttreatment. One week after treatment only 1%-2% of the flock still had facial cellulitis.

Mycoplasma gallisepticum infection results in numerous clinical signs including a reduction in egg production in laying chickens. Attempts to prevent mycoplasmosis have included vaccination with both killed and attenuated live M. gallisepticum strains. Live vaccines provide reduction in clinical signs and have been shown to replace indigenous strains when used in a consistent program for several placements. Antibiotic therapy is another option for controlling losses associated with mycoplasmosis. Therapeutic antibiotics with activity against mycoplasma approved for use in poultry include tetracyclines and tylosin. These drugs also are approved for feed efficiency when administered in the feed at levels below the therapeutic index for mycoplasma. The data presented here suggest that birds vaccinated with the live 6/85 strain of M. gallisepticum and then fed tylosin, at the approved level for feed efficiency, exhibit a serologic vaccine response similar to that of unmedicated birds but show improved feed efficiency.

The efficacy of tylosin phosphate for the treatment of necrotic enteritis (NE) was investigated in a floor pen study of 2,000 broiler chickens. A model in which Clostridium perfringens was administered in the feed on Days 14 to 16 was used to initiate an outbreak of NE. Treatments, allocated at the pen level in a randomized complete block design, consisted of five levels of tylosin phosphate (0, 50, 100, 200, or 300 ppm) administered in the feed on Days 15 to 22, following the identification of an outbreak of NE on Day 15. Mortality due to NE was significantly reduced (P < 0.05) for medicated birds at all dose levels of tylosin phosphate compared to unmedicated birds. Mean NE lesion scores on Day 17 were significantly reduced (P < 0.05) by all levels of tylosin treatment compared to those of unmedicated birds, decreasing linearly from 2.66 at 0 ppm to 0.38 at 100 ppm and 0 at higher doses. Tylosin at all levels provided improvement in Day 29 body weight, average daily gain, feed to gain ratio, and average daily feed intake compared to unmedicated birds. The results of this study provide evidence that tylosin phosphate, when administered in feed, is effective in the treatment of clinical outbreaks of NE in broiler chickens and suggest that the optimal dose for this purpose is 100 ppm.

In order to study the prophylactic and metaphylactic effect of antomicrobial growth promoters and ionophorous anticoccidials on the incidence of Cl. perfringens enterotoxaemia in chickens, experimental attempts were performed with 675 chickens in 27 trials. The birds were intraduodenally infected with Cl. perfringens type A (ATCC 3624). The following antimicrobial growth promoters and ionophore anticoccidials were used either on their own or in combination: avilamycin, narasin, monensin and tylosin. While infected and non-medicated trials showed an average incubation period of 1 week, clinical symptoms occurred 2-4 days later in infected and medicated birds. Avilamycin medicated birds had the longest incubation period. In the infected and non-medicated trials, a mortality rate of 16%-36% was noted within 3 weeks post infection. The avilamycin trials showed a mortality rate of 0-8% (0-2 birds died) and the narasin and monensin a mortality rate of 0-8%, respectively. In the combination groups (monensin + avilamycin or narasin + avilamycin), the mortality rate ranged from 0 to 4%. Tylosin showed a very good metaphylactic/therapeutic effect against Cl. perfringens enterotoxaemia. Following infection, medicated birds showed a significantly better bodyweight gain than the chickens, whose feeds had not been supplemented. From epidemiological point of view, the systematic prevention of coccidiosis is a key in the control of Cl. perfringens enterotoxaemia in chickens.

A virulent strain of Mycoplasma gallisepticum (MG) was used to infect groups of 40 2-day-old poults kept in separate pens of 10 each. Of the six groups, three were treated with separate concentrations of tilmicosin, one was treated with tylosin, one remained untreated, and a final group was not infected and not treated. Mortality, clinical signs, and gross lesions were significantly less (P < 0.001) in the uninfected and infected medicated groups than in the infected unmedicated group. Also, the mean body weight gain of poults surviving to the end of the experiment was greater (P < 0.005) in the uninfected and infected medicated groups. MG was not recovered from the uninfected birds, and, among the infected poults, it was recovered from significantly fewer (P < 0.05) poults in the medicated groups. Serologic results were negative for the uninfected group, and there were fewer positive reactors for the infected medicated than the infected unmedicated group. In consideration of these results, tilmicosin should prove to be a useful addition to the antimicrobials in the treatment of MG infection in poults.

This study was conducted to evaluate the efficacy of 5-day, "in water" tilmicosin medication for the prevention of experimental Mycoplasma gallisepticum (MG) disease in 10-day-old specific-pathogen-free (SPF) chickens. Birds were inoculated intratracheally and into the sinus with the MG R-P10 strain. A limited dose titration of the antibiotic over the expected effective range was included, using six groups of 60 birds each: UI: uninfected untreated group; IUT: infected untreated group; IT1 to IT4: four infected treated groups, which were administered 50, 100, 200, or 300 mg/liter of tilmicosin. The birds were given tilmicosin from 8 to 13 days of age and were inoculated at 10 days of age. The birds were observed for 11 days postchallenge before terminal postmortem examination was completed including, assessment of lesions and sampling for mycoplasma culture and serology. Body-weight gains of the different groups were compared. The results showed that tilmicosin medication at dose levels of 50-300 mg/liter significantly decreased growth losses and respiratory signs due to MG infection (P < 0.05). Significant reduction in air sac and peritonitis lesions were obtained by treatment with 100, 200 or 300 mg/liter for 5 days (P < 0.05). A significant reduction in the proportion of MG-culture-positive birds was obtained at a dose level of 50 mg/liter (P < 0.05). Increasing the dose resulted in a further decrease in the number of MG shedding chickens to the extent that with the two highest doses of tilmicosin, no bird was serologically positive on day 21, compared to 46/58 positively infected untreated birds (day 21).

The minimum inhibitory concentrations of tylosin tartrate and a new macrolid antimicrobial agent, tilmicosin, were assessed for six strains of Mycoplasma gallisepticum (MG) and three strains of Mycoplasma synoviae (MS) in vitro by the microbroth method. For four of the strains of MG, tilmicosin showed a slightly lower minimum inhibitory concentration (MIC) than did tylosin at both the initial reading (when pH 7.0 is first seen in the dilutions under test) and the final reading at 14 days of incubation. For one of the remaining strains, the MIC for tilmicosin was equal to or less than that for tylosin at the initial reading but greater at the final reading. For the other strain, the MIC for tilmicosin was greater than for tylosin, and for both of them the MICs were very much higher than for other strains. For the three strains of MS, there was little difference between the two drugs for one strain whereas the MIC for tilmicosin was slightly less for the other two groups. Groups of 30 chicks were infected with a virulent strain of MG and treated with either tylosin (0.5 g/liter) or tilmicosin (at concentrations of 0.125, 0.25 or 0.5 g/liter). One infected group was untreated and another group was uninfected and untreated. Clinical signs, mainly depression and nervous signs, were seen in two to five birds in the infected treated groups. In contrast, in the infected untreated group, 16 of 30 birds showed clinical signs. Mortality was significantly less in the infected treated groups compared with the infected untreated group (P < 0.001), and following infection there were significantly (P < 0.05) greater weight gains in the infected medicated groups. At necropsy the prevalence of gross lesions of the airsac walls was similar in all the infected medicated groups and was less than that for the infected unmedicated group. For the group on tylosin, MG was recovered from five chicks during life and from six dead chicks. The corresponding figures for the group receiving the lowest dose of tilmicosin were four for each; however, the organism was not recovered from the groups on the higher doses of tilmicosin either during life or from dead chicks. Serological results were negative for all groups except the infected untreated group, in which all three birds that were tested were positive.

The efficacy of danofloxacin was compared with that of tylosin in the control of induced mycoplasmosis. In three experiments, disease was induced in broiler chicks by intrapulmonary injection of field isolates of Mycoplasma gallisepticum (MG) originating from Brazil, a different isolate being used for each experiment. Starting the day after inoculation, groups of chicks were medicated for 3 days via the drinking water with danofloxacin (50 ppm) or tylosin (500 ppm) or were left as unmedicated controls. Chicks were observed for 21 days. A severe mycoplasmosis was induced in unmedicated birds, characterized by mortality, depression, and respiratory signs. Danofloxacin was highly efficacious in controlling this infection in all three experiments, whereas tylosin was efficacious in only one. This difference could be related directly to the reduced in vitro susceptibility to tylosin displayed by the two isolates of MG. In the two experiments where isolates were tylosin-resistant, danofloxacin was significantly (P < or = 0.05) superior to tylosin in reducing mortality, maintaining weight gain, and reducing the prevalence of air-sac lesions, isolation of MG, and seroconversion.

Experimental mycoplasmosis was induced in 1-day-old chicks by intrapulmonary inoculation of Mycoplasma gallisepticum (MG). This method of infection proved to be useful for evaluating the efficacy of antimicrobial medication, by measuring mortality, weight gain, pathological responses, frequency of reisolation of MG, and seroconversion. Using this model, the efficacies of danofloxacin (a novel fluoroquinolone) and tylosin were compared for two MG isolates, a reference isolate (the R-strain) and a field isolate from California. Danofloxacin administered in the water at 50 ppm for 3 days was equivalent to tylosin at 500 ppm for 3 days in the degree of control of mortality and maintenance of weight gain. Danofloxacin was superior to tylosin in preventing air-sac lesions, reducing the frequency of reisolation of MG, and preventing seroconversion in surviving birds.

Groups of chicks were infected with a virulent strain of Mycoplasma gallisepticum (MG) and treated with either danofloxacin or tylosin while one infected group was left untreated and a further group was uninfected and untreated. Control of clinical signs and mortality was better with danofloxacin than tylosin and there was significantly (P < 0.05) greater weight gain with danofloxacin at 21 days after infection. However at necropsy the prevalence of lesions of the airsac walls was similar in both groups. MG was recovered from fewer live chicks for the first week following treatment with danofloxacin, but at 2 weeks and at necropsy, at the termination of the experiment, it was recovered from a similar proportion of birds in both treated groups. This was reflected also in the serological results at the end of the trial.

Specific pathogen free day-old chicks were inoculated with a virulent strain of Mycoplasma gallisepticum. Birds received either danofloxacin (50 ppm), tylosin (500 ppm) or no medication in the drinking water from 24 hours after infection for three days. The effects of medication on mortality, weight gain, serology, lesions and reisolation of M gallisepticum 21 days following infection were studied. Treatment with danofloxacin and tylosin significantly decreased mortality and increased weight gain compared with infected unmedicated birds. Twenty-one days after infection, M gallisepticum was isolated from 96 per cent of unmedicated birds compared with only 6 per cent of danofloxacin-treated and 40 per cent of tylosin-treated birds, and the percentage showing positive serological tests was reduced from 100 per cent of unmedicated birds to 0 per cent of danofloxacin-treated and 29 per cent of tylosin-treated birds. In both cases, the proportion of positive birds from the danofloxacin-treated group was significantly lower than that from the tylosin-treated group. The occurrence of air sac lesions was also significantly lower in danofloxacin-treated than in tylosin-treated birds.

The efficacy of treatment with single dose administration of 5 drugs at different dosages to layer hens naturally infected with Mycoplasma gallisepticum was studied. The drugs were tiamulin, which was administered orally, tylosin (parenterally and orally), spiramycin (orally), long-acting oxytetracycline (parenterally) and tylosindihydrostreptomycin (parenterally). Cure was assessed by the absence of nasal discharge. The cure rate was significantly higher (P less than 0.05) in treated hens than in untreated hens, as early as 1 day after treatment. Remission for 33 days was achieved in 60% of hens treated with 100 mg oxytetracycline, in 100% of hens treated with 100 mg or 200 mg spiramycin, in 92% and 85% of hens treated with 100 mg tylosin, parenterally and orally, and in 89% and 88% of birds given 100 mg tiamulin and tylosin-dihydrostreptomycin, respectively.