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Objective To determine the clinical significance of sputum Pasteurella multocida in adults with structural lung disease by operationally distinguishing infection from colonization and describing outcomes of pathogen-directed therapy. Methods We performed a single-center, retrospective case study. Infection was defined a priori by new or worsening lower -respiratory symptoms at the time of culture, supported by inflammatory or radiologic changes; isolation without symptoms was classified as colonization. Two pulmonologists blinded to the clinical data reviewed the chest CTs scans. Antibiotic selection and clinical responses within 2-4 weeks were extracted from the charts. Results Seven adults (five women; mean age, 67.1 years) with structural airway disease were included. Middle lobe syndrome and diffuse panbronchiolitis were predominant, while bronchiectasis was present in two patients. Five of the seven patients (71.4%) reported regular dog/cat exposure. Sputum cultures were obtained for acute symptom exacerbations in four patients and for incidental imaging abnormalities in three. Three symptomatic patients received penicillin-class therapy and all improved. One symptomatic patient improved without antibiotics. No recent animal bites or scratches were reported. No severe treatment-related adverse events were observed. Conclusion In elderly patients with structural airway disease, sputum P. multocida during symptomatic episodes likely represents true infection and responds to targeted narrow-spectrum therapy, whereas asymptomatic isolates may reflect colonization. These observations provide a pragmatic framework to distinguish infection from colonization, support susceptibility-aligned narrow-spectrum management, and offer small-series evidence to inform antimicrobial stewardship in structural lung diseases.