ceftiofur and Disease-Models--Animal

Inflammatory and immune mechanisms play important roles in the pathogenesis of neuropathic pain. Ceftiofur, a third-generation cephalosporin, has anti-inflammatory effects by inhibiting tumor necrosis factor (TNF)-α, interleukin (IL)-1β, nuclear factor (NF)-κB, and mitogen-activated protein kinase (MAPK) signaling. This study aimed to investigate the effect of ceftiofur on hyperalgesia and allodynia in neuropathic rats and to define the possible contribution of immune mechanisms to this effect.. A neuropathic pain model was performed by ligating the right sciatic nerve. Mechanic hyperalgesia and allodynia were measured using an analgesia meter and dynamic plantar esthesiometer, respectively. Following sciatic nerve ligation, ceftiofur was administered intraperitoneally (10 and 20 mg/kg/day) for 14 days. The control group received saline. Pain thresholds were recorded pre- and postoperatively on days 3, 7, 10, and 14. Protein was extracted from lumbar spinal cord tissue on day 14, and TNF-α, IL-1β, p65 NF-κB, p38 MAPK, and inducible nitric oxide synthase (iNOS) were evaluated by Western blotting.. Neuropathic rats showed decreased pain thresholds in analgesia meter and esthesiometer measurements. Ceftiofur 20 mg/kg/day significantly alleviated hyperalgesia, but not allodynia, and the increased iNOS and IL-1β expression was attenuated in neuropathic rats at both doses while decreasing p38 MAPK expression only at 20 mg/kg/day. TNF-α and p65 NF-κB expression remained unchanged 14 days after surgery.. Ceftiofur has anti-inflammatory effects by decreasing iNOS, IL-1β, and p38 MAPK expression in lumbar spinal cord, and treatment of neuropathic rats with repeated doses of ceftiofur for 14 days results in antihyperalgesic effects.

Topics: Analgesics; Animals; Cephalosporins; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Functional Laterality; Gene Expression Regulation; Hyperalgesia; Male; MAP Kinase Signaling System; Neuralgia; NF-kappa B; Pain Measurement; Pain Threshold; Physical Stimulation; Rats; Rats, Wistar; Time Factors; Tumor Necrosis Factor-alpha

Economical, injectable antibiotics are beneficial when clinical manifestations of an animal model prevent the use of oral antibiotics. Ceftiofur crystalline-free acid (CCFA) is an injectable, sustained-release form of ceftiofur, a third-generation cephalosporin that is labeled for use in swine, cattle, and horses. Because CCFA is an economical, injectable antibiotic that could be of value for use in research dogs, the objective of this study was to determine the pharmacokinetic properties of CCFA in apparently healthy dogs and to determine the minimal inhibitory concentrations of ceftiofur for veterinary pathogens cultured during 2011 through 2014 from the respiratory system, integumentary system, and urinary system of dogs. The study population comprised of 5 dogs (age, 1 y; weight, 24.7 to 26.9 kg) that were deemed healthy after no abnormalities were found on physical exam, CBC analysis, and clinical chemistry panel. Each dog received CCFA at 5.0 mg/kg SC, and blood samples were collected before administration of CCFA and at 1, 4, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 h after injection. The maximal plasma concentration (mean ± 1 SD) of CCFA was 1.98 ± 0.40 μ g/mL, time to reach maximal concentration was 22.3 ± 8.9 h, half-life was 56.6 ± 16.9 h, and AUC0-last was 124.98 ± 18.45 μ g-h/mL. The minimal inhibitory concentrations of ceftiofur ranged from ≤ 0.25 to ≥ 8.0 μ g/mL; ceftiofur was most effective against Pasteurella spp., Proteus spp., and Escherichia coli haemolytica and least effective against Bordatella bronchiseptica, Enterococcus spp., and Pseudomonas aeruginosa.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Cephalosporins; Disease Models, Animal; Dogs; Female; Half-Life; Male; Microbial Sensitivity Tests

Infections are common following stroke and associated with worse outcome. Using an animal model of pneumonia, we assessed the effect of infection and its treatment on the immune response and stroke outcome.. Lewis rats were subjected to transient cerebral ischemia and survived for 4weeks. One day after stroke animals were exposed to aerosolized Staphylococcus aureus, Pseudomonas aeruginosa or saline. Antibiotics (ceftiofur or enrofloxacin) were started immediately after exposure or delayed for 3days. Behavioral tests were performed weekly. ELISPOT assays were done on lymphocytes from spleen and brain to assess autoimmune responses to myelin basic protein (MBP).. Among animals that received immediate antibiotic therapy, infection was associated with worse outcome in ceftiofur but not enrofloxacin treated animals. (The outcome with immediate enrofloxacin therapy was so impaired that further worsening may have been difficult to detect.) A delay in antibiotic therapy was associated with better outcomes in both ceftiofur and enrofloxacin treated animals. Infection was associated with an increased likelihood of developing Th1(+) responses to MBP in non-infarcted brain (OR=2.94 [1.07, 8.12]; P=0.04), and Th1(+) responses to MBP in spleen and non-infarcted brain were independently associated with a decreased likelihood of stroke recovery (OR=0.16 [0.05, 0.51; P=0.002 and OR=0.32 [0.12, 0.84]; P=0.02, respectively).. Infection worsens stroke outcome in ceftiofur treated animals and increases Th1 responses to MBP. These data may help explain how infection worsens stroke outcome and suggest that treatment of infection may contribute to this outcome.

Topics: Animals; Anti-Bacterial Agents; Antineoplastic Agents; Body Temperature; Body Weight; Cephalosporins; Cytokines; Disease Models, Animal; Enrofloxacin; Fluoroquinolones; Lymphocytes; Male; Myelin Basic Protein; Nervous System Diseases; Pneumonia; Rats; Rats, Inbred Lew; Staphylococcus aureus; Statistics, Nonparametric; Stroke

Uterine disease such as metritis is associated with multiple bacterial infections in the uteri after parturition. However, treatment of metritis is challenging due to considerably high antibiotic treatment failure rate with unknown reason. Recently, chitosan microparticles (CM) have been developed to exert broad spectrum antimicrobial activity against bacterial pathogens, including multi-drug resistant bacteria, without raising CM resistant mutants. In this study, we tested, using metagenomics analysis, if CM maintain strong antimicrobial activity against pathogenic bacteria such as Fusobacteriaceae and Bacteroidaceae in cow uteri and evaluated CM's potency as an alternative antimicrobial agent to cure metritis in cows. Here, we report that efficacy of CM treatment for metritis was comparable to the antibiotic ceftiofur, and CM greatly altered uterine microflora of sick animals to healthy uterine microflora. Among uterine bacteria, CM significantly decreased Fusobacterium necrophorum, which is known pathogenic bacteria within the uterus. Taken together, we observed the broad spectrum antimicrobial activity of CM in vivo with an animal model, and further evaluated treatment efficacy in cows with metritis, providing insights into promising use of CM as an alternative antimicrobial agent for controlling uterine disease.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Bacteroidaceae Infections; Cattle; Cephalosporins; Chitosan; Disease Models, Animal; Female; Fusobacteriaceae Infections; Fusobacterium necrophorum; Humans; Treatment Outcome; Uterine Diseases; Uterus

Despite the high number of antibiotics used for the treatment of infectious disease in animals, the development of slow release formulations presents a significant challenge, particularly in using novel biomaterials with low cost. In this report, we studied the pharmacokinetics, toxicity, and therapeutic activity of ceftiofur-PHBV (ceftiofur-poly(3-hydroxybutyrate-co-3-hydroxyvalerate)) in rats. The pharmacokinetic study demonstrated a sustained release of ceftiofur into the bloodstream, with detectable levels over the minimum inhibitory concentration for at least 17 days after a single intramuscular injection of ceftiofur-PHBV (10 mg/kg weight). In addition, the toxicological evaluation of biochemical, hematological, and coagulation blood parameters at the therapeutic dose demonstrated the safety of ceftiofur-PHBV, with no adverse effects. In addition, ceftiofur-PHBV exhibited a therapeutic effect for a longer time period than the nonencapsulated ceftiofur in rats challenged with Salmonella Typhimurium. The slow release of ceftiofur from the ceftiofur-PHBV, its low toxicity in the blood parameters evaluated, and the efficacy in the rats infected with Salmonella Typhimurium make ceftiofur-PHBV a strong candidate for biotechnological applications in the veterinary industry.

Topics: Animals; Cephalosporins; Disease Models, Animal; Dose-Response Relationship, Drug; Erythrocytes; Injections, Intramuscular; Male; Microbial Sensitivity Tests; Polyesters; Rats; Rats, Sprague-Dawley; Salmonella Infections; Salmonella typhimurium; Structure-Activity Relationship

The influence of ceftiofur on immune responses has been suggested by results of in vitro studies. This effect was studied using a murine model that measured mortality and early cytokine responses after challenge with endotoxin. To investigate the treatment of endotoxic mice with ceftiofur, mice were pretreated with ceftiofur at different times before and after challenge with a lethal dose of 30 mg/kg lipopolysaccharide (LPS). We found that 20 mg/kg ceftiofur had a significant protective effect and reduced the mortality of mice at early stages. To further understand the mechanism of action of ceftiofur, we examined plasma cytokine levels. Mice treated with LPS alone showed markedly increased plasma levels of TNF-alpha, IL-1beta, IL-6 and IL-10, whereas mice pretreated with 20 mg/kg ceftiofur showed significantly decreased plasma levels of TNF-alpha, IL-1beta and IL-6, but increased plasma levels of IL-10. These results support the idea that ceftiofur has a beneficial effect on LPS-induced endotoxemia caused by LPS through its modulation of cytokine levels. This confirms the effect of ceftiofur for the treatment of endotoxemia, which is caused by a Gram-negative bacterial infection.

Topics: Animals; Anti-Bacterial Agents; Cephalosporins; Cytokines; Disease Models, Animal; Endotoxemia; Female; Interleukin-10; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Time Factors; Tumor Necrosis Factor-alpha