Freddy Haesebrouck

There are not many data available on antibiotics used solely in animals and almost exclusively for growth promotion. These products include bambermycin, avilamycin, efrotomycin, and the ionophore antibiotics (monensin, salinomycin, narasin, and lasalocid). Information is also scarce for bacitracin used only marginally in human and veterinary medicine and for streptogramin antibiotics. The mechanisms of action of and resistance mechanisms against these antibiotics are described. Special emphasis is given to the prevalence of resistance among gram-positive bacteria isolated from animals and humans. Since no susceptibility breakpoints are available for most of the antibiotics discussed, an alternative approach to the interpretation of MICs is presented. Also, some pharmacokinetic data and information on the influence of these products on the intestinal flora are presented.

Salmonella Enteritidis (SE) has been the major cause of the food-borne salmonellosis pandemic in humans over the last 20 years, during which contaminated hen's eggs were the most important vehicle of the infection. Eggs can be contaminated on the outer shell surface and internally. Internal contamination can be the result of penetration through the eggshell or by direct contamination of egg contents before oviposition, originating from infection of the reproductive organs. Once inside the egg, the bacteria need to cope with antimicrobial factors in the albumen and vitelline membrane before migration to the yolk can occur. It would seem that serotype Enteritidis has intrinsic characteristics that allow an epidemiological association with hen eggs that are still undefined. There are indications that SE survives the attacks with the help of antimicrobial molecules during the formation of the egg in the hen's oviduct and inside the egg. This appears to require a unique combination of genes encoding for improved cell wall protection and repairing cellular and molecular damage, among others.

The incidence of Clostridium perfringens-associated necrotic enteritis in poultry has increased in countries that stopped using antibiotic growth promoters. Necrotic enteritis and the subclinical form of C. perfringens infection in poultry are caused by C. perfringens type A, producing the alpha toxin, and to a lesser extent type C, producing both alpha toxin and beta toxin. Some strains of C. perfringens type A produce an enterotoxin at the moment of sporulation and are responsible for foodborne disease in humans. The mechanisms of colonization of the avian small intestinal tract and the factors involved in toxin production are largely unknown. It is generally accepted, however, that predisposing factors are required for these bacteria to colonize and cause disease in poultry. The best known predisposing factor is mucosal damage, caused by coccidiosis. Diets with high levels of indigestible, water-soluble non-starch polysaccharides, known to increase the viscosity of the intestinal contents, also predispose to necrotic enteritis. Standardized models are being developed for the reproduction of colonization of poultry by C. perfringens and the C. perfringens-associated necrotic enteritis. One such model is a combined infection with Eimeria species and C. perfringens. Few tools and strategies are available for prevention and control of C. perfringens in poultry. Vaccination against the pathogen and the use of probiotic and prebiotic products has been suggested, but are not available for practical use in the field at the present time. The most cost-effective control will probably be achieved by balancing the composition of the feed.

Clostridium perfringens-induced necrotic enteritis and related subclinical disease have become economically significant problems for the broiler industry. Fortunately, scientific interest in this topic has grown: new C. perfringens virulence factors have been discovered and new insight gained about the pathogenesis of necrotic enteritis. It has been shown that alpha toxin, for a long time thought to be the key virulence factor, is not essential for the development of the disease. Moreover, it is now clearly established that only certain C. perfringens strains are capable of inducing necrotic enteritis under specific conditions that predispose to the disease and they constitute only a minority in the intestinal tract of healthy chickens. A novel pore-forming toxin, NetB, has been identified in these virulent avian C. perfringens strains. Using a gene knockout mutant, it has been shown that NetB is a critical virulence factor in the pathogenesis of necrotic enteritis in broilers. In addition to toxin production, other factors have been described that contribute to the ability of certain C. perfringens strains to cause necrotic enteritis in broilers. It has been suggested that proteolytic enzymes play an important role in the initial stages of necrotic enteritis since the villi are first affected at the level of the basement membrane and the lateral domain of the enterocytes. In field outbreaks of necrotic enteritis, a single clone of C. perfringens is dominant in intestines of all affected birds, as opposed to the mixture of different C. perfringens strains that can be isolated from healthy bird intestines. It has been proposed that bacteriocin production is responsible for the dominance of a single strain in necrotic enteritis cases. Furthermore, it has been shown that virulent strains are more able to adhere to extracellular matrix molecules than non-virulent strains. The current knowledge on the pathogenesis of the disease has been summarized in this short review.

Salmonella is a human pathogen that is commonly found in poultry products. It is possible to decrease chicken carcass and egg contaminations by adding organic acids to the feed or drinking water at appropriate times. Medium-chain fatty acids are more antibacterial against Salmonella than short-chain fatty acids. The antibacterial effect of these acids is species specific. Bacteria that are unable to decrease intracellular pH accumulate organic acid anions in accordance with the pH gradient across their cell membranes. The short-chain fatty acid butyrate specifically down-regulates expression of invasion genes in Salmonella spp. at low doses. Also medium-chain fatty acids and propionate decrease the ability of Salmonella spp. to invade epithelial cells, in contrast to acetic acid. Because not all bacteria are affected in a similar fashion by organic acids, it may be possible to use probiotic and prebiotic bacteria to achieve beneficial effects. If diets can be designed to stimulate organic acid production in the caecum, it may be possible to control Salmonella spp. via even easier and more cost-effective measures, compared with addition of acids to feed or drinking water. Utilisation d'acides organiques pour combattre les salmonelles chez les volailles: mécanisme d'efficacité Les salmonelles sont, pour l'homme, des agents pathogènes qui se retrouvent communément dans les produits avicoles. Il est possible de diminuer les contaminations des carcasses de poulet et des æufs en ajoutant des acides organiques aux aliments ou à l'eau de boisson à des moments appropriés. Les acides gras à chaîne moyenne sont plus antibactériens contre les salmonelles que les acides gras à chaîne courte. L'effet antibactérien de ces acides est spécifique d'espèce. Les bactéries qui ne sont pas capables de diminuer le pH intracellulaire accumulent les anions d'acides organiques suivant le gradient de pH au travers de leurs membranes cellulaires. Le butyrate, acide gras à chaîne courte, diminue spécifiquement l'expression des gènes d'invasion chez Salmonella spp., à doses faibles. De même, les acides gras à chaîne moyenne et le propionate diminuent la capacité de Salmonella spp. d'envahir les cellules épithéliales, contrairement à l'acide acétique. Du fait que toutes les bactéries ne sont pas affectées de la même façon par les acides organiques, il peut être possible d'utiliser des probiotiques et des prébiotiques pour atteindre des effets bénéfiques. Si des régimes alimentaires peuvent être définis pour stimuler la production d'acides organiques dans les cæca, il peut être possible de contrôler Salmonella spp. de façon encore plus facile et plus rentable, par rapport à l'addition d'acides dans l'aliment ou dans l'eau de boisson. Die Verwendung von organischen Säuren zur Bekämpfung von Salmonellen beim Geflügel: Erklärung des Wirkungsmechanismus Salmonellen sind humane Infektionserreger, die häufig in Geflügelprodukten gefunden werden. Durch die Zugabe von organischen Säuren zum Futter oder Trinkwasser zum richtigen Zeitpunkt ist es möglich, die Kontamination von Hühnerschlachtkörpern und -eiern zu verringern. Mittellangkettige Fettsäuren besitzen eine stärkere antibakterielle Wirkung gegen Salmonella als kurzkettige Fettsäuren. Der antibakterielle Effekt dieser Säuren ist speziesspezifisch. Bakterien, die nicht in der Lage sind, den intrazellulären pH zu senken, akkumulieren organische Säureanionen entsprechend dem pH-Gradienten über ihre Zellmembranen. Speziell die kurzkettige Buttersäure reguliert die Exprimierung von Invasionsgenen von Salmonella spp. in geringen Dosen runter. Auch mittellangkettige Fettsäuren und Proprionatsäure verringern im Gegensatz zu Essigsäure die Fähigkeit von Salmonella spp. in Epithelzellen einzudringen. Da nicht alle Bakterien in gleicher Weise von organischen Säuren beeinflusst werden, kann der Einsatz von pro- und präbiotischen Bakterien eine positive Auswirkung haben. Wenn Diäten zusammengesetzt werden können, um die Bildung von organischen Säuren im Zäkum zu stimulieren, wird im Vergleich mit dem Zusatz von Säuren zu Futter oder Trinkwasser sogar eine leichtere und kostengünstigere Salmonellenbekämpfung möglich sein. El uso de ácidos orgánicos para combatir frente a Salmonella en avicultura: una explicación mecánica de su eficacia Salmonella es un patógeno humano que se aísla frecuentemente en productos avícolas. Es posible reducir la contaminación de las canales y huevos mediante la adición de ácidos orgánicos en el pienso o en el agua de bebida en momentos apropiados. Los ácidos grasos de cadena media tienen mayor efecto antibacteriano frente a Salmonella que los ácidos grasos de cadena corta. El efecto antibacteriano de estos ácidos es especie-específico. Aquellas bacterias que son incapaces de reducir el pH intracelular acumulan aniones de ácidos orgánicos en función del gradiente de pH a través de sus membranas celulares. El butirato, ácido graso de cadena corta, regula específicamente a la baja la expresión de genes invasivos en Salmonella spp. a dosis bajas. También otros ácidos grasos de cadena media y los propionatos reducen la capacidad de Salmonella spp. de invadir células epiteliales, en comparación con el ácido acético. El uso de bacterias como prebióticos y probióticos para obtener efectos beneficiosos es posible debido a que los ácidos orgánicos no las afectan por igual. Así pues si pudieran diseñarse dietas para estimular la producción de ácidos grasos en el ciego, se lograría el control de Salmonella spp. mediante medidas sencillas y con mejor relación coste-eficacia, en comparación con la adición de ácidos al pienso o al agua de bebida.