Efficacy of trimethoprim‐sulfadoxine against Escherichia coli in a tissue cage model in calves

Abstract

Tissue cages implanted subcutaneously in calves were infected with Escherichia coli. Twenty-four hours later, the calves were treated either with single doses of 2.5 + 12.5 or 5 + 25 mg/kg trimethoprim (TMP) + sulfadoxine (SDX) or with five doses of 7.5 + 37.5 mg/kg TMP + SDX at 12-h intervals. In addition, one cage in each of three calves in the highest dose group was infected 3 h after initiation of treatment. Untreated calves were kept as controls. Concentrations of TMP and SDX in plasma and tissue cage fluid (TCF) and counts of viable bacteria in TCF were determined. In the highest dose group, concentrations of TMP in TCF remained above the minimum inhibitory concentration of the test strain for 94-101 h and peak to minimum inhibitory concentration (MIC) ratio was close to 10. In spite of this, an effect of treatment was noted only in cages infected after initiation of treatment. In vitro studies and analysis of thymidine content in serum and TCF from calves suggest that levels of thymidine in TCF are high enough to antagonize the antibacterial effect of TMP. The results indicate that soft tissue infections in secluded infection sites of calves are refractory to treatment with TMP + SDX.

Silver sulfadoxinate: Synthesis, structural and spectroscopic characterizations, and preliminary antibacterial assays in vitro

“…Besides the antimalarial activity, the sulfadoxine-pyrimethamine hybrid is also active against the parasite Toxoplasma gondii [15] and is considered as primary prophylaxis of pneumonia caused by Pneumocyctis carinii [16][17][18] and toxoplasmatic encephalitis in patients infected with HIV [17,18]. Sulfadoxine is also used in combination with trimethoprim to treat different bacterial infections in animals as horses and calves, being active against Gram-negative and Gram-positive bacteria [19][20][21].…”

Synergistic Antimicrobial Activities of Folic Acid Antagonists and Nucleoside Analogs

“…Greko and colleagues previously showed that tissue infections in secluded infection sites of calves were refractory to treatment with trimethoprim-sulfadoxine due to elevated thymidine concentrations (13). Thymidine concentrations were previously reported to be high in the blood of several animals (24).…”

“…However, the effects of these antibiotics can be antagonized by the bacterial utilization of extracellular thymidine (2,13,18,33,36,39). Various bacteria have the ability to use an alternative pathway by the uptake of extracellular thymidine and the subsequent intracellular phosphorylation to dTMP by thymidine kinase (19,39).…”

Bioavailability and Pharmacokinetics of Sulphadiazine, N4-acetylsulphadiazine and Trimethoprim following Intravenous and Intramuscular Administration of a Sulphadiazine/Trimethoprim Combination in Sheep

“…In general, a microorganism is considered susceptible when displaying a TMP/SDZ MIC lower than 0.5/9.5 mg/ml (Prescott, 2000). However, synergy is observed over a wide range of ratios, provided that both drugs are present at levels above their MICs (Bushby, 1980;Greko et al, 2002). Following i.v.…”

“…The pharmacokinetics of SDZ and/or TMP have been most extensively studied in cattle and calves (Clarke et al, 1989;Kaartinen et al, 1999Kaartinen et al, , 2000Greko et al, 2002). Studies in other species, such as swine (Nielsen and Rasmussen, 1975a,b;Garwacki et al, 1996), dogs and cats (Craig and White, 1976;Sigel et al, 1981), horses (Brown et al, 1983;Bogan et al, 1984;Van Duijkeren et al, 1994a, Gustafsson et al, 1999, poultry (Lo« scher et al, 1990;Batzias et al, 2000;Baert et al, 2003), rabbits (Ladefoged, 1977) and ¢sh (Nouws et al, 1993), have also been performed.…”