Comparison of functional-oil blend and anticoccidial antibiotics effects on performance and microbiota of broiler chickens challenged by coccidiosis.

This study aimed to compare the effects of different levels of cashew nutshell liquid (CNSL) and castor oil (CNSL-castor oil) with growth-promoting antibiotics associated with anticoccidials in broiler chickens challenged with coccidiosis. In this work, 2520 one-day-old male broiler chicks (Cobb) were randomly assigned to 84 pens, containing 30 birds each. The experimental design was completely randomized, with seven treatments: enramycin (8 ppm), virginiamycin (16.5 ppm), and tylosin (55 ppm); different doses of CNSL-castor oil (0.5, 0.75, and 1.00 kg/t); and a control diet (without additives). All treatments received semduramicin + nicarbazin (500 g/t; Aviax® Plus) from 0 to 28 d and monensin sodium (100 ppm; Elanco) from 29 to 35 days of age, when the feed was without antibiotics. The challenge was introduced at 14 days of age by inoculating broiler chickens with sporulated Eimeria tenella, Eimeria acervulina, and Eimeria maxima oocysts via oral gavage. In addition to performance parameters, intestinal contents were collected at 28 and 42 days of age for microbiota analysis by sequencing the 16s rRNA in V3 and V4 regions using the Illumina MiSeq platform. Taxonomy was assigned using the SILVA database (v. 138) with QIIME2 software (v. 2020.11). After one week of challenge, the broilers that received tylosin had a higher body weight gain (BWG) than those in the control group (p < 0.05), while the other treatments presented intermediate values. At 28 d, the BWG was lower for the control, CNSL-Castor oil 0.5 kg/t, enramycin, and virginiamycin treatments than that in the tylosin treatment. The inclusion of CNSL-Castor oil at concentrations of 0.75 and 1 kg/t acted as an intermediate treatment (p < 0.05). For alpha diversity, using the Shannon index, it was possible to observe the effect of age, with substantial diversity at 42 d. The Firmicutes phylum had the highest abundance, with values between 84.33% and 95.16% at 42 d. Tylosin showed better performance indices than other treatments. CNSL-castor oil treatments with concentrations of 0.75 and 1 kg/t showed similar results to those of enramycin and virginiamycin. Furthermore, CNSL-castor oil acted as a modulator of intestinal microbiota, reducing the abundance of pathogenic bacteria.

Comparative evaluation of different therapeutic protocols for contagious caprine pleuropneumonia in Himalayan Pashmina goats.

Therapeutic management of contagious caprine pleuroneumonia (CCPP) involves mostly the use of oxytetracycline followed by enrofloxacin and rarely tylosin. In many parts of the world including India, the former antibiotics are commonly available than the latter. Therefore, prolonged use of the same leads to the development of antibiotic resistance and decreased efficacy of drug. Besides, inflammatory and allergic pathogenesis of CCPP envisages combination therapy. In this study, we evaluated the effectiveness of the combination therapy using different antibiotics (oxytetracycyline @ 10: group I, enrofloxacin @ 5 group II, and tylosin: group III, @ 10 mg/kg body weight), along with anti-inflammatory (meloxicam @ 0.5 mg/kg) and anti-allergic (pheneramine maleate @ 1.0 mg/kg) drugs. These drugs were given intramuscularly at the interval of 48 h for four times in three test groups (n = 10) of Pashmina goats, viz. groups I, II, and III, respectively, affected with CCPP. Group IV (n = 10) was kept as healthy control when group V (n = 10) treated with oxytetracycline @ 10 mg/kg alone was used as positive control. Clinical signs, clinical parameters, pro-inflammatory cytokine (tumor necrosis factor alpha (TNF-α)), and oxidative stress indices (total oxidant status (TOS), total antioxidant status (TAS)) were evaluated at hours 0, 48, 96, and 144 of experimental trial. Tylosin-based combination therapy resulted in a rapid and favorable recovery resulting in restoration of normal body temperature (102.46 ± 0.31 °F), respiration rate (16.30 ± 0.79 per minute), and heart rate (89.50 ± 2.63 per minute) compared to the oxytetracycline (102.95 ± 0.13, 21.30 ± 1.12, 86.00 ± 2.33, respectively) and enrofloxacin (102.97 ± 0.19, 21.00 ± 1.25, 90.00 ± 2.58, respectively) treated groups. By hour 144, all the groups showed restoration of clinical parameters of normal health and diminishing signs of CCPP, viz. fever, dyspnea, coughing, nasal discharge, weakness, and pleurodynia. Significant (P ≤ 0.05) decrease in levels of TNF-α and non-significant (P > 0.05) decrease in levels of TOS and an increase in levels of TAS were noted from hour 0 to 144 in all the test groups. Within the groups, no significant (P > 0.05) change was noted in TNF-α, TOS, and TAS levels; however, TNF-α levels were comparatively lower in group III. Hematological parameters did not differ significantly (P > 0.05). From these findings, it can be inferred that tylosin-based combination therapy is relatively better for early, rapid, and safe recovery besides minimizing inflammatory and oxidative cascade in CCPP affected Pashmina goats compared to oxytetracycline- and enrofloxacin-based therapies.

Tylosin injectable for the treatment of porcine proliferative enteropathy in experimentally inoculated pigs / Tilosina injetável no tratamento da enteropatia proliferativa suína em leitões experimentalmente inoculados

Porcine proliferative enteropathy (PPE) is one of the most common enteric diseases in growing and finishing pigs. PPE is characterized by reduced growth performance, accompanied or not by diarrhea. PPE is highly prevalent in several countries of the Americas, Europe and Asia, causing high economic losses in swine herds. The most common form of PPE control in pigs is antibiotic therapy. The objective of this study was to evaluate a new product based on tylosin injectable (Eurofarma Laboratórios S.A.) to control PPE in experimentally inoculated animals. Sixty 5-week-old pigs with mean weight of 9.5kg were divided into two experimental groups of 30 animals: medication and control. All pigs were challenged with Lawsonia intracellularis, the etiologic agent of PPE, on day zero. Fecal score, body condition score, and behavior were daily evaluated. Pigs were weighted on days -2, 13 and 21 of the experiment. Pigs in the Medication Group received tylosin injectable 13 days after inoculation, in three doses with a 12-hour interval between them. Pigs in the Control Group received injectable saline solution following the same protocol. In the Control Group, 23pigs presented with diarrhea before day 13. After day 13, the number of diarrheic animals in this group was reduced to 17. In the Medication Group, 26 pigs presented with diarrhea in the initial period, and in the period after medication, only 11 animals had diarrhea. The score of gross intestinal PPE lesions in the Medication Group was lower than that in the Control Group (p=0.031). The Medication Group also showed lower score for Lawsonia intracellularis antigen-labeling by immunohistochemistry compared with that of the Control Group (p=0.032), showing lower level of infection. These results demonstrate that tylosin injectable (Eurofarma Laboratórios S.A.), administrated in three doses (1mL/20kg) every 12 hours, was effective for the control of PPE in experimentally inoculated pigs.(AU)

Enteropatia proliferativa suína (EPS), causada pela bactéria Lawsonia intracellularis, é uma das doenças entéricas mais comuns em suínos de recria e terminação. A EPS caracteriza-se por redução no desempenho dos animais, acompanhada ou não por diarreia. É uma doença altamente prevalente em diversos países da América, Europa e Ásia, provocando elevados prejuízos econômicos nos rebanhos suínos. A forma de controle da EPS mais adotada em rebanhos suínos é a antibioticoterapia. O objetivo deste estudo foi avaliar um novo produto à base de tilosina (Eurofarma Laboratórios S.A.) na forma injetável para controlar a EPS em animais experimentalmente inoculados. Foram utilizados 60 leitões, de cinco semanas de idade, com peso médio de 9,5kg, divididos em dois grupos experimentais (n=30), medicados e não medicados. Todos os leitões foram desafiados com Lawsonia intracellularis no dia zero. Avaliações clínicas de escore fecal, escore corporal e comportamento foram realizadas diariamente além da pesagem individual dos animais realizada nos dias -2, 13 e 21 do experimento. Os leitões do grupo medicado receberam tilosina injetável 13 dias após a inoculação em três doses com intervalo de 12 horas cada. Já os leitões do grupo não medicado receberam solução salina injetável com o mesmo protocolo. O grupo não medicado apresentou 23 animais com diarreia antes do dia 13 e 17 após este período. No grupo medicado, 26 animais apresentaram diarreia previamente à medicação e apenas 11 após a medicação a partir do dia 13. Os leitões medicados apresentaram extensão de lesão macroscópica, caracterizada por espessamento de mucosa intestinal, menor em comparação com o grupo não medicado (p=0,031). A imunomarcação para Lawsonia intracellularis foi menor no grupo medicado (p<0,032), mostrando redução no grau de infecção por L. intracellularis nos animais medicados. Estes resultados demonstram que a tilosina injetável (Eurofarma Laboratórios S.A.) (1mL/20kg) em três doses, a cada 12 horas, foi eficaz no tratamento da enteropatia proliferativa suína em animais experimentalmente inoculados.(AU)

Whole-flock, metaphylactic tilmicosin failed to eliminate contagious ovine digital dermatitis and footrot in sheep: a cluster randomised trial.

The aim of this study was to evaluate the clinical success of whole-flock systemic tilmicosin and enhanced biosecurity in eliminating active contagious ovine digital dermatitis (CODD) from sheep flocks. Thirty flocks in the UK were randomly allocated to receive either treatment as usual (as per the farmer's normal routine) or whole-flock treatment with tilmicosin, together with isolation and extended treatment of clinically affected individuals and isolation and treatment of purchased sheep during the study period. All flocks were visited once at onset of the trial to examine all sheep. One year later, all sheep were re-examined to determine the presence/absence of clinical lesions. The primary outcome was the clinical elimination of CODD from flocks. Secondary outcomes were reduction in prevalence of CODD, clinical elimination of footrot and reduction in prevalence of footrot. The analysis included 11 control flocks and 13 intervention flocks, with initially 3460 and 4686 sheep, respectively. For CODD: at follow-up, in the intervention group, 6/13 (46 per cent) flocks had a prevalence of zero compared with 1/11 (9 per cent) in the control group (P=0.12). For footrot: at follow-up, no flocks had a prevalence of zero. Therefore, the intervention is not recommended for the elimination of CODD or footrot in the UK.

Effects of the macrolide drug tylosin on chronic diarrhea in rhesus macaques (Macaca mulatta).

Diarrhea is the gastrointestinal disease most frequently encountered in captive rhesus macaques. The precise pathogenic mechanisms underlying chronic diarrhea in nonhuman primates are not well understood, but a persistent inflammatory component has been implicated strongly. This study evaluated the inflammatory changes in the colon of macaques with diarrhea and assessed the efficacy of a 10-d course of tylosin in a cohort of 21 animals with chronic diarrhea. Stool quality was evaluated daily, and fecal consistency was scored. Colonoscopies were performed; biopsy samples were characterized histologically and assayed for expression of TNFalpha mRNA. Blood samples collected pre-, mid-, and post-treatment were assayed for C-reactive protein (CRP). The results indicated that 63% of the animals receiving tylosin showed improvement in stool quality, compared with 10% in the sham-treated group. Histologically, 82% of animals in the tylosin-treated group had a reduction in the severity of colonic lesions post-treatment, compared with 40% of animals in the sham group. The amount of TNFalpha mRNA before treatment did not differ from that afterward in either tylosin- or sham-treated animals. CRP levels serially decreased in tylosin-treated monkeys; the average post-treatment CRP value for tylosin-treated animals was 11.96 +/- 3.86 microg/ml compared with 26.48 +/- 4.86 microg/ml for sham-treated controls. In conclusion, tylosin significantly improved the fecal consistency score, significantly decreased colonic inflammation, and significantly decreased serum CRP levels post-treatment in rhesus macaques with chronic diarrhea.

Susceptibility of Mycobacterium avium sbsp paratuberculosis to monensin sodium or tilmicosin phosphate in vitro and resulting infectivity in a murine model.

This study was designed to determine the susceptibility in vitro and infectivity of 1 field isolate of Mycobacterium avium sbsp paratuberculosis after exposure to monensin sodium and tilmicosin phosphate. Minimum inhibitory concentrations (0.39 microg monensin sodium/mL; 1.60 microg tilmicosin phosphate/mL) were determined in quintuplicate. Organisms were then incubated with 3 different concentrations of each medication for 3 different lengths of time, then washed and resuspended in sterile physiologic saline and injected intraperitoneally into mice that were genetically susceptible to infection. Mice were euthanatized 50 d later and the number of hepatic granulomas was used as the indicator of infectivity. Neither time of incubation nor concentration of medication had any effect on the infectivity of the organisms. Monensin sodium significantly reduced the number of hepatic granulomas in genetically susceptible mice while tilmicosin phosphate did not. Antimycobacterial activity of monensin sodium suggests that the role of monensin in the control of bovine paratuberculosis should be evaluated further.

Tilmicosin-induced bovine neutrophil apoptosis is cell-specific and downregulates spontaneous LTB4 synthesis without increasing Fas expression.

The pathology of bacterial pneumonia, such as seen in the bovine lung infected with Mannheimia haemolytica, is due to pathogen virulence factors and to inflammation initiated by the host. Tilmicosin is a macrolide effective in treating bacterial pneumonia and recent findings suggest that this antibiotic may provide anti-inflammatory benefits by inducing polymorphonuclear neutrophilic leukocyte (PMN) apoptosis. Using an in vitro bovine system, we examined the cell-specificity of tilmicosin, characterized the changes in spontaneous leukotriene B4 (LTB4) synthesis by PMN exposed to the macrolide, and assessed its effects on PMN Fas expression. Previous findings demonstrated that tilmicosin is able to induce PMN apoptosis. These results were confirmed in this study by the Annexin-V staining of externalized phosphatidylserine and the analysis with flow cytometry. The cell-specificity of tilmicosin was assessed by quantification of apoptosis in bovine PMN, mononuclear leukocytes, monocyte-derived macrophages, endothelial cells, epithelial cells, and fibroblasts cultured with the macrolide. The effect of tilmicosin on spontaneous LTB4 production by PMN was evaluated via an enzyme-linked immunosorbent assay. Finally, the mechanisms of tilmicosin-induced PMN apoptosis were examined by assessing the effects of tilmicosin on surface Fas expression on PMN. Tilmicosin-induced apoptosis was found to be at least partially cell-specific, as PMN were the only cell type tested to die via apoptosis in response to incubation with tilmicosin. PMN incubated with tilmicosin under conditions that induce apoptosis spontaneously produced less LTB4, but did not exhibit altered Fas expression. In conclusion, tilmicosin-induced apoptosis is specific to PMN, inhibits spontaneous LTB4 production, and occurs through a pathway independent of Fas upregulation.

Anti-inflammatory benefits of tilmicosin in calves with Pasteurella haemolytica-infected lungs.

OBJECTIVES: To determine whether tilmicosin alters neutrophil infiltration or function, induces neutrophil apoptosis, and affects accumulation of leukotriene B4 (LTB4) or tumor necrosis factor-alpha (TNF-alpha) in lungs of calves experimentally infected with Pasteurella haemolytica. ANIMALS: 12 weight-ranked Holstein calves. PROCEDURE: Calves were given 25% propylene glycol vehicle (n = 5) or tilmicosin (10 mg/kg of body weight; n = 6) subcutaneously, 18 hours and 15 minutes before intratracheal infection with 2 x 10(8) P haemolytica organisms. Two unmanipulated calves served as controls in some experiments. Rectal temperatures were recorded 15 minutes before, and at 3-hour intervals after infection for 24 hours. Samples obtained from bronchoalveolar lavage performed 3 and 24 hours after infection were used to assess colonization by P haemolytica, and neutrophil infiltration. Neutrophil phagocytosis of P haemolytica, membrane leakage as determined by trypan blue exclusion, oxidative function as determined by nitro blue tetrazolium reduction, and apoptosis, using electron microscopy and DNA fragmentation ELISA, were determined. SOluble TNF-alpha and LTB4 were measured from supernatants from bronchoalveolar lavage samples, using ELISA. RESULTS: Treatment with tilmicosin resulted in significant (P < 0.05) clearance of P haemolytica and neutrophil apoptosis at 3 hours, and decreased concentration of LTB4 at 24 hours. Rectal temperatures, neutrophil infiltration, phagocytosis, oxidative functions, membrane leakage, and soluble TNF-alpha concentrations were not significantly affected by tilmicosin. CONCLUSION: Tilmicosin effectively controlled P haemolytica infection, induced neutrophil apoptosis, reduced pulmonary inflammation, and did not affect neutrophil infiltration or function. CLINICAL RELEVANCE: By inducing neutrophil apoptosis, tilmicosin prevents further amplification of inflammatory injury in P haemolytica-infected lungs.

Control of proliferative enteropathy in growing/fattening pigs using growth promoters.

The aim of this study was to evaluate the effect of different antibiotics used as growth promoters on the control of porcine intestinal adenomatosis when administered in weaning, growing and fattening pig diets, according to Annex I of the European Union directive (70/524/EEC and its subsequent amendments to date) for the use of feed additives. On a farm with a previous history of proliferative enteropathy outbreaks, 648 weaned piglets (23 days old) were divided into nine experimental groups according to bodyweight and sex ratio, each group comprising four pens with 18 pigs in each pen. One group served the trial as a negative (unmedicated) control: another (the positive control) received monensin via feed at 100 p.p.m. up to the end of the growing phase (107 days old) and 50 p.p.m. up to slaughter age (156 days old). The remaining seven groups were offered feed with the addition of the following antibiotics: virginia-mycin (50-20 p.p.m.), avilamycin (40-20 p.p.m.), spiramycin (50-20 p.p.m.), zinc bacitracin (50-10 p.p.m.), avoparcin (40-20 p.p.m.), tylosin (40-20 p.p.m.) and salinomycin (60-30 p.p.m.), respectively. The performance of the pigs in the positive control group was very satisfying and among the highest in the trial, verifying earlier field studies. As a general conclusion it seems that all tested growth promoters had a beneficial effect compared with the untreated control, indicated by the decrease of mortality rate, the elimination of diarrhoeal incidence and the enhancement of growth performance, although the proliferative enteropathy control achieved by each substance was not always satisfactory. More specifically, the antibiotic growth promoters tested can be scaled according to their total efficacy as follows: 1. Salinomycin, tylosin, spiramycin; 2. Virginiamycin, zinc bacitracin, avilamycin; and 3. Avoparcin. Finally, it is considered that part of the growth promotion efficacy of the tested substances is due to their potential capacity to control porcine intestinal adenomatosis; thus, in future growth performance trials, the disease background of the trial farms must be examined, especially for porcine enteropathy challenges.