Evaluation of sulbactam plus ampicillin for treatment of experimentally induced Klebsiella pneumoniae lung infection in foals

Andrew M. Hoffman From the Departments of Clinical Studies (Hoffman, Viel, Staempfli), Veterinary Microbiology and Immunology (Muckle), and Veterinary Pathology (Yager), Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada N1G 2W1.

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Laurent Viel From the Departments of Clinical Studies (Hoffman, Viel, Staempfli), Veterinary Microbiology and Immunology (Muckle), and Veterinary Pathology (Yager), Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada N1G 2W1.

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Catherine A. Muckle From the Departments of Clinical Studies (Hoffman, Viel, Staempfli), Veterinary Microbiology and Immunology (Muckle), and Veterinary Pathology (Yager), Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada N1G 2W1.

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Julie S. Yager From the Departments of Clinical Studies (Hoffman, Viel, Staempfli), Veterinary Microbiology and Immunology (Muckle), and Veterinary Pathology (Yager), Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada N1G 2W1.

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Henry R. Staempfli From the Departments of Clinical Studies (Hoffman, Viel, Staempfli), Veterinary Microbiology and Immunology (Muckle), and Veterinary Pathology (Yager), Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada N1G 2W1.

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Summary

Efficacy of sulbactam, a β-lactamase inhibitor, in combination with ampicillin, was evaluated for treatment of experimentally induced pneumonia caused by β-lactam-resistant Klebsiella pneumoniae. Infection was experimentally induced in 18 healthy weanling foals that were randomly allocated to 3 treatment groups: sulbactam plus ampicillin (s/a, 3.3 and 6.6 mg/kg of body weight, respectively), ampicillin (6.6 mg/kg), or vehicle only. Foals were treated daily for 7 days; the observer was unaware of treatment status. Compared with ampicillin and vehicle, treatment with s/a resulted in a statistically significant (P < 0.05) decrease in severity of pneumonia, with regard to bronchoalveolar lavage cytologic findings (decreased total cell and neutrophil numbers, and increased lymphocyte numbers) and extent of macroscopic lesions in lung tissue of the noninoculated regions. Marked trends toward improvement of s/a-treated foals were observed for quantitative results of bacteriologic culture of bronchoalveolar lavage fluid samples (P < 0.07), macroscopic pathologic features of the whole lung (P < 0.1), and histopathologic variables (P < 0.07), compared with ampicillin- and vehicle-treated foals. Treatment effects were not observed for radiographic, hematologic, and blood gas abnormalities that resulted from infection. In conclusion, the combination of sulbactam plus ampicillin was found to have synergistic effects in vivo, to reduce the extent and severity of experimentally induced gram-negative lung infection in foals.

Summary

Efficacy of sulbactam, a β-lactamase inhibitor, in combination with ampicillin, was evaluated for treatment of experimentally induced pneumonia caused by β-lactam-resistant Klebsiella pneumoniae. Infection was experimentally induced in 18 healthy weanling foals that were randomly allocated to 3 treatment groups: sulbactam plus ampicillin (s/a, 3.3 and 6.6 mg/kg of body weight, respectively), ampicillin (6.6 mg/kg), or vehicle only. Foals were treated daily for 7 days; the observer was unaware of treatment status. Compared with ampicillin and vehicle, treatment with s/a resulted in a statistically significant (P < 0.05) decrease in severity of pneumonia, with regard to bronchoalveolar lavage cytologic findings (decreased total cell and neutrophil numbers, and increased lymphocyte numbers) and extent of macroscopic lesions in lung tissue of the noninoculated regions. Marked trends toward improvement of s/a-treated foals were observed for quantitative results of bacteriologic culture of bronchoalveolar lavage fluid samples (P < 0.07), macroscopic pathologic features of the whole lung (P < 0.1), and histopathologic variables (P < 0.07), compared with ampicillin- and vehicle-treated foals. Treatment effects were not observed for radiographic, hematologic, and blood gas abnormalities that resulted from infection. In conclusion, the combination of sulbactam plus ampicillin was found to have synergistic effects in vivo, to reduce the extent and severity of experimentally induced gram-negative lung infection in foals.

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