Flavomycin is a phosphoglycolipid antibiotic, which is used exclusively as a growth- promoting feed additive. Existing data, from both in vitro and in vivo ruminal studies, give conflicting results regarding its mode of action, as well as no clear microbiological basis for the observed responses. Studies however do indicate that the principal site of action of the antibiotic is the rumen. From the available data, flavomycin appears to promote growth in a manner distinct from that of other feed antibiotics, for which the growth-promoting mechanisms have been elucidated. This study aimed to characterise the effect that flavomycin has on the microflora of the rumen, allowing its growth promoting mechanism in ruminants to be determined. In vitro analysis demonstrated that flavomycin has only antibacterial activity, as ruminal species of protozoa, fungi and archaea were unaffected by the antibiotic. Of the ruminal bacterial species tested, Fusobacterium necrophorum, Fibrobacter spp. and certain hyper-ammonia producing (HAP) bacteria (Atopobium oviles, Desulfomonas sp. and Peptostreptococcus anaerobius) were highly sensitive to the antibiotic. The sensitivity of the Fibrobacter spp. to flavomycin suggested that flavomycin is likely to select for a cellulolytic bacterial flora comprised predominantly of Ruminococcus spp., as has been previously proposed on the basis of in vitro fermentation studies. In vivo, suppression of ruminal numbers of F. necrophorum and flavomycin sensitive HAP bacteria occurred as a result of flavomycin supplementation. It was demonstrated that these bacterial populations were highly variable, between individual sheep and days respectively, suggesting why previous studies produced conflicting results. Assessment of ruminal fermentation parameters demonstrated that flavomycin caused a significant decrease in the production of ruminal ammonia, which could be directly attributed to decreased numbers of ruminal HAP bacteria. A small increase in the ruminal concentration of lactate also occurred, which con-elated with the suppression of ruminal numbers of the lactate utilising F. necrophorum. No change in the balance of individual volatile fatty acids (VFA) occurred, however total VFA production was significantly decreased. This was likely to be due to the total viable anaerobic bacterial counts being lower during flavomycin supplementation, although this result was not statistically significant. Uncultured rumen bacteria were also implicated in the growth promoting mechanism of flavomycin. Molecular investigation of the rumen bacterial population by denaturing gradient gel electrophoresis (DGGE) demonstrated that several changes occurred, which correlated with flavomycin supplementation. Analysis of the sequence data obtained from excised DGGE bands highlighted that the majority of the operational taxonomic units (OTU) detected were represented by presently uncultured species of bacteria, of which almost half had not been previously identified. Identification of the flavomycin sensitive bacterial populations was not possible, however, due to the recovery of multiple sequences from individual DGGE bands. Existing bacterial 16S rDNA sequence data, from published ruminal clone libraries, also demonstrated the poor cultural representation of rumen bacterial diversity, with only 10% of the OTU detected being represented by cultured bacterial species. Based on these results, flavomycin has the ability to increase the efficiency of dietary protein utilisation, although the role of uncultured bacteria in the growth promoting mechanism of the antibiotic is not clear. Protein retention in the rumen is increased as a consequence of decreased deamination by ruminal HAP bacteria. F. necrophorum has the ability to attach to and damage rumen epithelium, as well as being the principal aetiological agent in the development of liver abscesses. Suppression of F. necrophorum is likely to decrease metabolic and immune burdens within the animal, as well as potentially reducing the rate of rumen wall tissue turnover. The use of flavomycin as a feed additive is to be banned in Europe in 2005. However, it is not known if presently available feed additives or treatments will be able to act as an effective replacement for this antibiotic. Characterisation of an adaptive resistance mechanism against flavomycin, in the ruminal bacterium Prevotella bryantii, demonstrated that cross-resistance to therapeutic antibiotics can occur. As a result of this finding, and the interest in development of phosphoglycolipid antibiotics for therapeutic application, it can be concluded that the withdrawal of the use of a flavomycin as a feed additive is a wise precautionary measure to ensure the long-term efficacy of this class of antibiotics.

A flavomicina é um antimicrobiano registrado no Ministério da Agricultura do Brasil e que tem sido amplamente utilizado na avicultura e suinocultura. Seu uso foi intenso até o final dos anos 1990, sendo este reduzido posteriormente. Este produto está registrado como promotor de crescimento até a dose máxima de 2 ppm no Brasil. A definição desta dose provêm de trabalhos executados há muitas décadas e, portanto, é possível que as doses que otimizem seu uso sejam diferentes na avicultura atual, especialmente em um cenário de limitadas ferramentas para melhora de desempenho de frangos de corte. O objetivo deste trabalho foi reavaliar a utilização da flavomicina em frangos de corte a partir de um experimento dose-resposta. Foram utilizados 900 frangos de corte machos Cobb x Cobb 500 de um dia de idade, divididos em 5 tratamentos com 12 unidades experimentais cada. Os tratamentos foram constituídos de doses crescentes de flavomicina formuladas com níveis similares de EMAn e nutrientes baseados em níveis utilizados pela indústria brasileira: 0, 2, 4, 8 e 16 ppm de flavomicina. A avaliação de desempenho foi feita semanalmente até os 42 dias com avaliações de ganho de peso, conversão alimentar corrigida para mortalidade, consumo de ração e mortalidade. No período de 1 a 21 dias de idade, as dosagens ótimas calculadas pela equação de regressão foram de 16 ppm , 12,17 ppm e 14,68 ppm para consumo de ração, conversão alimentar e ganho de peso, respectivamente. De 22 a 42 dias, as dosagens foram de 10,31 e 9,83 ppm para conversão alimentar e ganho de peso. Pela equação de regressão do período acumulado de 1 a 42 dias, houve uma melhora crescente até o platô de inclusão de 10,9 e 10,14 ppm, para ganho de peso e conversão alimentar. O estudo nos mostra que, nas condições experimentais, o desempenho de modernas linhagens de frangos de corte podem ser maximizados de dosagens que variam de 9,83 até 16 ppm, acima dos padrões estabelecidos na legislação brasileira. / Flavophospholipol is an antimicrobial registered in Ministério of Agricultura of Brazil that has been widely used in poultry and swine production. Its use was intense until the end of 1990, which was later reduced. This product is registered as a growth promoter until the maximum dosis of 2 ppm in Brazil. These doses derived from research performed many decades ago and, therefore, this dose is likely to different from the one that optimizes broiler performance, especially in a scenario of limited tools for improvements of performance of broilers. The objective of this study was to reassess the use of flavophospholipol for broilers in a dose-response trial. A total of nine hundred male Cobb x Cobb 500 broilers were placed across five treatments with 12 replications each. The treatments consisted of increasing doses of flavophospholipol: 0, 2, 4, 8, 16 ppm. The diets were formulated with similar levels of metabolizable energy based on levels and nutrients used by the Brazilian industry. Performance evaluation was done weekly until the day 42. The evaluated parameters were: body weight gain, feed conversion ratio corrected for mortality, feed intake and percentage of mortality. In the period equation were 16 ppm, 12.17 ppm and 14.68 ppm for feed intake, feed conversion ratio and body weight gain, respectively. From 22 to 42 days, the estimated doses were 10.31 and 9.83 ppm for feed conversion and body weight gain. In the cumulative period from 1 to 42 days it was found an increased improvement until the plateau which was 10.9 and 10.14 ppm, for body weight gain and feed conversion ratio. The study showed that under the experimental conditions used, the performance of modern broilers could be optimized from 9.83 to 16 ppm, above the standards established by Brazilian legislation.

A flavomicina é um antimicrobiano registrado no Ministério da Agricultura do Brasil e que tem sido amplamente utilizado na avicultura e suinocultura. Seu uso foi intenso até o final dos anos 1990, sendo este reduzido posteriormente. Este produto está registrado como promotor de crescimento até a dose máxima de 2 ppm no Brasil. A definição desta dose provêm de trabalhos executados há muitas décadas e, portanto, é possível que as doses que otimizem seu uso sejam diferentes na avicultura atual, especialmente em um cenário de limitadas ferramentas para melhora de desempenho de frangos de corte. O objetivo deste trabalho foi reavaliar a utilização da flavomicina em frangos de corte a partir de um experimento dose-resposta. Foram utilizados 900 frangos de corte machos Cobb x Cobb 500 de um dia de idade, divididos em 5 tratamentos com 12 unidades experimentais cada. Os tratamentos foram constituídos de doses crescentes de flavomicina formuladas com níveis similares de EMAn e nutrientes baseados em níveis utilizados pela indústria brasileira: 0, 2, 4, 8 e 16 ppm de flavomicina. A avaliação de desempenho foi feita semanalmente até os 42 dias com avaliações de ganho de peso, conversão alimentar corrigida para mortalidade, consumo de ração e mortalidade. No período de 1 a 21 dias de idade, as dosagens ótimas calculadas pela equação de regressão foram de 16 ppm , 12,17 ppm e 14,68 ppm para consumo de ração, conversão alimentar e ganho de peso, respectivamente. De 22 a 42 dias, as dosagens foram de 10,31 e 9,83 ppm para conversão alimentar e ganho de peso. Pela equação de regressão do período acumulado de 1 a 42 dias, houve uma melhora crescente até o platô de inclusão de 10,9 e 10,14 ppm, para ganho de peso e conversão alimentar. O estudo nos mostra que, nas condições experimentais, o desempenho de modernas linhagens de frangos de corte podem ser maximizados de dosagens que variam de 9,83 até 16 ppm, acima dos padrões estabelecidos na legislação brasileira. / Flavophospholipol is an antimicrobial registered in Ministério of Agricultura of Brazil that has been widely used in poultry and swine production. Its use was intense until the end of 1990, which was later reduced. This product is registered as a growth promoter until the maximum dosis of 2 ppm in Brazil. These doses derived from research performed many decades ago and, therefore, this dose is likely to different from the one that optimizes broiler performance, especially in a scenario of limited tools for improvements of performance of broilers. The objective of this study was to reassess the use of flavophospholipol for broilers in a dose-response trial. A total of nine hundred male Cobb x Cobb 500 broilers were placed across five treatments with 12 replications each. The treatments consisted of increasing doses of flavophospholipol: 0, 2, 4, 8, 16 ppm. The diets were formulated with similar levels of metabolizable energy based on levels and nutrients used by the Brazilian industry. Performance evaluation was done weekly until the day 42. The evaluated parameters were: body weight gain, feed conversion ratio corrected for mortality, feed intake and percentage of mortality. In the period equation were 16 ppm, 12.17 ppm and 14.68 ppm for feed intake, feed conversion ratio and body weight gain, respectively. From 22 to 42 days, the estimated doses were 10.31 and 9.83 ppm for feed conversion and body weight gain. In the cumulative period from 1 to 42 days it was found an increased improvement until the plateau which was 10.9 and 10.14 ppm, for body weight gain and feed conversion ratio. The study showed that under the experimental conditions used, the performance of modern broilers could be optimized from 9.83 to 16 ppm, above the standards established by Brazilian legislation.

A flavomicina é um antimicrobiano registrado no Ministério da Agricultura do Brasil e que tem sido amplamente utilizado na avicultura e suinocultura. Seu uso foi intenso até o final dos anos 1990, sendo este reduzido posteriormente. Este produto está registrado como promotor de crescimento até a dose máxima de 2 ppm no Brasil. A definição desta dose provêm de trabalhos executados há muitas décadas e, portanto, é possível que as doses que otimizem seu uso sejam diferentes na avicultura atual, especialmente em um cenário de limitadas ferramentas para melhora de desempenho de frangos de corte. O objetivo deste trabalho foi reavaliar a utilização da flavomicina em frangos de corte a partir de um experimento dose-resposta. Foram utilizados 900 frangos de corte machos Cobb x Cobb 500 de um dia de idade, divididos em 5 tratamentos com 12 unidades experimentais cada. Os tratamentos foram constituídos de doses crescentes de flavomicina formuladas com níveis similares de EMAn e nutrientes baseados em níveis utilizados pela indústria brasileira: 0, 2, 4, 8 e 16 ppm de flavomicina. A avaliação de desempenho foi feita semanalmente até os 42 dias com avaliações de ganho de peso, conversão alimentar corrigida para mortalidade, consumo de ração e mortalidade. No período de 1 a 21 dias de idade, as dosagens ótimas calculadas pela equação de regressão foram de 16 ppm , 12,17 ppm e 14,68 ppm para consumo de ração, conversão alimentar e ganho de peso, respectivamente. De 22 a 42 dias, as dosagens foram de 10,31 e 9,83 ppm para conversão alimentar e ganho de peso. Pela equação de regressão do período acumulado de 1 a 42 dias, houve uma melhora crescente até o platô de inclusão de 10,9 e 10,14 ppm, para ganho de peso e conversão alimentar. O estudo nos mostra que, nas condições experimentais, o desempenho de modernas linhagens de frangos de corte podem ser maximizados de dosagens que variam de 9,83 até 16 ppm, acima dos padrões estabelecidos na legislação brasileira. / Flavophospholipol is an antimicrobial registered in Ministério of Agricultura of Brazil that has been widely used in poultry and swine production. Its use was intense until the end of 1990, which was later reduced. This product is registered as a growth promoter until the maximum dosis of 2 ppm in Brazil. These doses derived from research performed many decades ago and, therefore, this dose is likely to different from the one that optimizes broiler performance, especially in a scenario of limited tools for improvements of performance of broilers. The objective of this study was to reassess the use of flavophospholipol for broilers in a dose-response trial. A total of nine hundred male Cobb x Cobb 500 broilers were placed across five treatments with 12 replications each. The treatments consisted of increasing doses of flavophospholipol: 0, 2, 4, 8, 16 ppm. The diets were formulated with similar levels of metabolizable energy based on levels and nutrients used by the Brazilian industry. Performance evaluation was done weekly until the day 42. The evaluated parameters were: body weight gain, feed conversion ratio corrected for mortality, feed intake and percentage of mortality. In the period equation were 16 ppm, 12.17 ppm and 14.68 ppm for feed intake, feed conversion ratio and body weight gain, respectively. From 22 to 42 days, the estimated doses were 10.31 and 9.83 ppm for feed conversion and body weight gain. In the cumulative period from 1 to 42 days it was found an increased improvement until the plateau which was 10.9 and 10.14 ppm, for body weight gain and feed conversion ratio. The study showed that under the experimental conditions used, the performance of modern broilers could be optimized from 9.83 to 16 ppm, above the standards established by Brazilian legislation.