A Rat Model of Prolonged Pulmonary Infection Due to NontypableHaemophilus influenzae

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Abstract
Pulmonary colonization and infection with nontypable (unencapsulated) Haemophilus influenzae (NTHI) occurs commonly in the setting of chronic lung diseases. Because the study of NTHI pulmonary infection in animal models has been limited by the rapid clearance of organisms, a model of persistent pulmonary infection was developed. Groups of rats were inoculated by trans-tracheal instillation of viable NTHI suspended in broth or semisolid agar. Some rats had received hexamethylphosphoramide (HMP) in drinking water before inoculation to cause respiratory epithelial mucosal damage. Groups of animals were sacrificed serially. Lungs were cultured quantitatively and their gross and microscopic anatomy examined. NTHI was recovered in small quantities from few broth-inoculated rats after the first day of infection and in none after Day 7. In contrast, NTHI was recovered from the majority of animals and in greater amounts through 2 wk after agar-borne inoculation. HMP pretreatment further enhanced recovery through 4 wk after inoculation with an agar vehicle. The pulmonary inflammatory reaction was brief in broth-inoculated rats. The longer persistence of gross and histologic changes seen in agar-infected lungs paralleled the enhanced recovery of NTHI. Abscess formation occurred at 7 to 14 days in some agar-inoculated animals. Thus pulmonary inoculation of NTHI in a viscous vehicle resulted in perpetuation of infection and inflammatory response, and previous damage to respiratory mucosal epithelium induced by HMP further enhanced such infection.