ceftiofur and Pneumonia

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

Ceftiofur is a new broad-spectrum, third-generation cephalosporin antibiotic for veterinary use. Our laboratory has previously been reported that ceftiofur can modulate early cytokine responses and increase mouse survival in endotoxemia. In the present study, we investigated the effect of ceftiofur on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in vivo. Mice were pretreated with ceftiofur 1h before challenge with a dose of 0.5mg/kg LPS. Mice treated with LPS alone showed marked increased TNF-alpha, IL-6, and IL-8 levels in the bronchoalveolar lavage fluid (BALF). When pretreated with 30mg/kg of ceftiofur, the TNF-alpha, IL-6, and IL-8 levels were significantly decreased. In addition, the W/D ratio of the lung tissue and the number of total cells, neutrophils and macrophages in the BALF significantly decreased at 8h after pretreatment with ceftiofur. Furthermore, ceftiofur markedly attenuated the LPS-induced histological alteration. These studies indicate that ceftiofur significantly decreases the inflammation in a murine model of LPS-mediated ALI and may represent a novel prevention strategy for nonspecific inflammation in the lungs.

Topics: Acute Lung Injury; Animals; Bronchoalveolar Lavage; Cell Count; Cephalosporins; Cytokines; Humans; Lipopolysaccharides; Lung; Macrophages; Male; Mice; Mice, Inbred BALB C; Neutrophils; Pneumonia