Adjunctive efficacy of granulocyte colony-stimulating factor on treatment of Pseudomonas aeruginosa pneumonia in neutropenic and non-neutropenic hosts

Objectives: Granulocyte colony-stimulating factor (G-CSF) stimulates proliferation of neutrophils and enhances their phagocytic and microcidal activity. Increasing resistance to existing antibacterials and the dearth of new alternatives have complicated the treatment of Gram-negative infections. The aim of this study was to evaluate the efficacy of G-CSF in the treatment of Pseudomonas aeruginosa pneumonia when administered in combination with ceftazidime in both neutropenic and non-neutropenic hosts. Methods: A group of mice were rendered neutropenic with cyclophosphamide. Pneumonia was induced by intratracheal instillation of similar to5 x 10(7) cfu/mL and similar to5 x 10(9) cfu/mL (LD100) of the organism to neutropenic and non-neutropenic mice, respectively. Two hours after inoculation, the mice received normal saline and 5% dextrose, G-CSF (300 mug/kg per day x 3 days), ceftazidime (2000 mg/kg x 2 doses) or a combination of G-CSF and ceftazidime. Survival was monitored at different time points for 5 days. Results: Treatment with G-CSF showed a dose-dependent increase in survival from 50 to 300 mug/kg. In neutropenic mice, survival was markedly better in the G-CSF + ceftazidime group compared with controls (P = 0.0001), G-CSF (P = 0.0002) or ceftazidime (P = 0.0172). In non-neutropenic mice, survival in the G-CSF + ceftazidime group (20%) was significantly higher than in the control and G-CSF groups (P = 0.0001) but not significantly higher than ceftazidime alone (9%) (P > 0.05). Conclusions: G-CSF administered in combination with antibiotic after onset of severe P. aeruginosa pneumonia may improve therapeutic outcome and this suggests a new treatment option in the management of pneumonia especially in neutropenic patients.