trimethoprim--sulfamethoxazole-drug-combination and Actinobacillus-Infections

The pharmacokinetics of two sulfonamide/trimethoprim combinations were investigated after intravenous administration to clinically healthy pigs and to the same pigs following a challenge with Actinobacillus pleuropneumoniae toxins. Endobronchial challenge with A. pleuropneumoniae toxins resulted in fever, increased white blood cell counts and decreased water and feed consumption. Healthy, as well as febrile, pigs were given sulfadimethoxine (SDM) or sulfamethoxazole (SMX) intravenously at a dose of 25 mg/kg b.w. in combination with 5 mg trimethoprim (TMP) per kg body weight. The pharmacokinetic parameters of the sulfonamides as well as their main metabolites (acetyl sulfonamides) were not significantly different in healthy and febrile pigs. In healthy and pneumonic pigs, the mean elimination half-lives of SDM were 12.9 h and 13.4 h, respectively, those of SMX 2.5 h and 2.7 h, respectively, and those of TMP 2.8 h and 2.6 h, respectively. Distribution volumes in healthy and febrile pigs of SDM and SMX varied between 0.2 and 0.4 L/kg, and those of TMP between 1.1 and 1.6 L/kg. The mean AUC of TMP was decreased and the volume of distribution and total body clearance of TMP were increased in febrile pigs. Protein binding of the drugs and metabolites studied were not significantly changed after toxin-induced fever. The extent of protein binding of SDM, SMX and TMP was in the range 94-99%, 45-56% and 40-50%, respectively. Based on knowledge of in vitro antimicrobial activity of the drug combinations against A. pleuropneumoniae it was concluded that after intravenous administration of the dose administered (30 mg/kg of the combination preparations) to healthy and pneumonic pigs, plasma concentrations of SMX and TMP were above the concentration required for growth inhibition of 50% of A., pleuropneumoniae strains for approximately 16 h, whereas bacteriostatic plasma concentrations of SDM were still present after TMP had been eliminated from plasma. Because of similar elimination half-lives of SMX and TMP in pigs this combination is preferred to the combination of SDM with TMP.

Topics: Actinobacillus Infections; Actinobacillus pleuropneumoniae; Animals; Anti-Bacterial Agents; Bacterial Toxins; Chromatography, High Pressure Liquid; Disease Models, Animal; Drinking; Drug Combinations; Eating; Half-Life; Injections, Intravenous; Male; Metabolic Clearance Rate; Pneumonia, Bacterial; Protein Binding; Regression Analysis; Sulfadimethoxine; Swine; Swine Diseases; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

A patient is described in whom there developed a pulmonary infiltrate and constrictive pericarditis caused by a combined Actinomyces and Actinobacillus actinomycetemcomitans infection, presumably originating from his poor dentition. The diagnosis was only made following repeated thoracotomy. After surgery, long-term treatment with antibiotics led to complete clinical recovery. None the less, some months later he was found to have a brain abscess which resolved during a further course of antibiotics. The variable clinical picture of actinomycosis is discussed, as well as the role of other bacteria frequently associated with actinomycotic infection, in particular Actinobacillus actinomycetemcomitans. The therapeutic implications are described.

Topics: Actinobacillus Infections; Actinomyces; Actinomycosis; Adult; Aggregatibacter actinomycetemcomitans; Brain Abscess; Humans; Male; Pericarditis, Constrictive; Pneumonia; Trimethoprim, Sulfamethoxazole Drug Combination

Two sanitation trials showed that it was possible to rear serologically negative animals from pigs on a breeding farm infected with Actinobacillus pleuropneumoniae serotype 2. This was achieved by the medication of sows and piglets during the farrowing-house period and by isolating the piglets from the infected stock of pigs immediately after weaning. Medication of the sows consisted in administering sulphamethoxazole-trimethoprim in the drinking water for a period from five days before to eight days after farrowing. The piglets were treated by injections of sulphadoxine-trimethoprim on days 3, 10, 17 and 24.

Topics: Actinobacillus Infections; Animals; Animals, Newborn; Breeding; Carrier State; Drug Combinations; Female; Sulfadoxine; Swine; Swine Diseases; Trimethoprim, Sulfamethoxazole Drug Combination