Oxytetracycline and Ketoprofen in the Treatment of “Shipping Fever”

Shipping Fever, also called bovine respiratory disease complex or pneumonic pasteurellosis, is an important respiratory disease of cattle that appears in animals from six months of age, usually after suffering stress caused by transportation, which may include mixing and grouping with other batches of animals of the same age during transportation, in the market and arrival at the finishing farm (Caswell, 2006; Kasimanickam, 2010). As a result of this stress, certain opportunistic bacteria take advantage of the momentary decrease in the defenses to multiply and produce infection; among these bacteria are Mannhemia haemolytica and Pasteurella multocida as the most important (Andrews, 2004; Rice et al, 2007; Gasque, 2008).

Most cases of Shipping Fever occur in the first 30 days of entrance to the fattening farm and most cases are seen at least 10 days after arrival (Kasimanickam, 2010).  Shipping Fever is clinically characterized by an acute exudative bronchopneumonia with toxemia and quite fast breathing, moderate to severe pyrexia and anorexy and a large amount of exudate (Quiroz, 2007; Gasque, 2008). Morbidity of pneumonic pasteurellosis varies between 5% and 10% and in some cases it can produce 1% mortality of the susceptible population (Andrews, 2004).  It is so that this disease causes great economic losses through the reduction of daily weight gain, food efficiency, and overall performance of meat calves, disregarding the cost generated by the treatment for the affected animals (Caswell, 2006; Kasimanickam, 2010).

The diagnosis of this disease is given based on the clinical signs mentioned above, characteristic of this disease, and generally based on responses to treatment; however, in case there are deaths, a necropsy to the animal should be made and lung tissue samples must be sent to laboratory for isolation of Mannhemia haemolytica and Pasteurella multocida (Quiroz, 2007; Kasimanickam, 2010). Early recognition and proper treatment application significantly improve final performance. It is so that the application of a general purpose antimicrobial is recommended (tetracyclines, cephalosporins or quinolones) and the addition of a nonsteroid antiinflammatory to speed up the recovery of the animal (Andrews, 2004; Quiroz, 2007; Gasque, 2008; Kasimanickam, 2010)

Oxytetracycline is an antibiotic belonging to the tetracycline family and has bacteriostatic action on numerous Gram-positive and Gram-negative microorganisms responsible for respiratory infections, among others, and has shown great effectiveness in cases of Shipping Fever. It acts altering protein synthesis by inhibiting the metabolism of glutamic acid, slowing the development and growth of the microorganism, but it can have a bactericidal effect when reaching high concentrations in tissues (Prescott and Baggot, 1993; Sumano and Ocampo, 2006).

Oxytetracycline is absorbed in a very good way when applied in an intramuscular injection and plasma can be detected in 15 minutes, reaching its highest level in one hour and maintaining therapeutic figures for maximum 12 hours. Its distribution is homogeneous throughout the body, but mainly in the liver, spleen and lungs; therefore is highly effective in pneumonic pasteurellosis problems. Its distribution enables to reach to fetal circulation with a concentration of approximately 50% of concentration in maternal blood (Sumano and Ocampo, 2006).  Tetracyclines generally are excreted via kidneys, where it can recover up to 80% of the applied dose without modifications, and via gastrointestinal tract when entering the enterohepatic circulation (Ghizlane, 2006)

Ketoprofen is an antipyretic analgesic, nonsteroidal anti-inflammatory belonging to the family of organic acids and derived from propinionic acid. It acts by inhibiting cyclooxygenase of the arachidonic acid metabolism, leading to a decreasing production of prostaglandins. Inhibits both cyclooxygenase 1 (COX1) and cyclooxygenase 2 (COX2), with some variation of degree between species, preventing the formation of prostaglandins and inflammation they cause. Its antipyretic properties are based in the reduction of prostaglandin levels in the hypothalamus. Ketoprofen also disrupts the function of certain mediators of inflammation, such as bradykinin, thus preventing its effect in peripheral nerve endings (TUSPC, 2004)

As can be observed, both mentioned drugs: oxytetracycline as antimicrobial and ketoprofen as antipyretic analgesic and anti-inflammatory are ideal for the treatment of Shipping Fever because of their individual properties. Ruiz (2007) test the combination of both active substances (Proxifen23 L.A. ®) in 100 bovines diagnosed with pneumonia in Huancavelica, Perú, with excellent results. In this experiment the recovery of 100% of the animals was observed within the first 48 hours of drug application, showing most animals a rapid recovery of febrile and infectious condition, without any kind of adverse reactions.

Currently large number of veterinary laboratories provides a great deal of options and presentations for treatment using these drugs; however for practicality reasons and to decrease stress, the ideal would be to administer both compounds together in a single injection.

Andrews AH, Blowey RW, Boey H, Eddy RG. 2004. Bovine Medicine Diseases and Husbandry of Cattle. 2º Ed. Blackwell Science Ltd. Caswell J. 2006. Preventing shipping fever pneumonia in calves. Beef cattle research council. Gasque R. 2008. Enciclopedia Bovina. Universidad Nacional Autónoma de México, Facultad de Medicina Veterinaria y Zootecnia, México.

Ghizlane EK. 2006. Thesis for the degree of doctor in pharmacology: “Pharmacokinetics and efficacy of  Oxytetracycline after intramuscular administration in cattle. Tisular depletion”. Universidad Autónoma de

Barcelona. Facultad de Medicina Veterinaria.

Kasimanickam R. 2010. Bovine Respiratory Disease “Shipping Fever” in Cattle.WashingtonState

University Extension & WSU College of Veterinary Medicine. Prescott, JF.; Baggot D. 1993. Antimicrobial Therapy in Veterinary Medicine. Second edition. p 557-558 Quiroz MA. 2007. Pasteurelosis neumónica. Clínica de los bovinos. Universidad Nacional Autónoma de México, Facultad De Medicina Veterinaria. Rice JA, Carrasco-Medina L, Hodgins DC, Shewen PE. 2007. Mannheimia haemolytica and bovine respiratory disease. Animal Health Research Reviews Volume 8 Issue 02, pp 117-128. Ruiz F, Rodriguez L, Gutierrez L. 2007. Evaluación de Tolerancia y Eficacia de una Solución Inyectable sobre la base de Dihidrato de Oxitetraciclina y ketoprofeno en un vehículo de larga (Proxifen 23 L.A.) para el tratamiento de neumonías diagnosticados en campo en bovinos y ovinos en Huancavelica – Perú. Sumano HS, Ocampo L. 2006. Farmacología Veterinaria. MacGraw-Hill Interamericana. 3º Edición The United States Pharmaceutical Convention (TUSPC). 2004. Ketoprofen: Veterinary—Systemic.